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Allergic asthma is a complex inflammatory disorder predominantly orchestrated by T helper 2 (Th2) lymphocytes. The anti-inflammatory protein Clara Cell 10-kDa (CC10), also known as secretoglobin family 1A member 1 (SCGB1A1), shows promise in modulating respiratory diseases. However, its precise role in asthma remains unclear. This study examines the potential of CC10 to suppress allergic asthma inflammation, specifically assessing its regulatory effects on Th2 cell responses and dendritic cells (DCs). Lower CC10 levels in asthma were observed and correlated with increased IgE and lymphocytes. Cc10 -/- mice exhibited exacerbated allergic airway inflammation marked by increased inflammatory cell infiltration, Th2 cytokines, serum antigen-specific IgE levels, and airway hyperresponsiveness (AHR) in house dust mite (HDM)-induced models. Conversely, recombinant CC10 significantly attenuated these inflammatory responses. Intriguingly, CC10 did not directly inhibit Th cell activation but significantly downregulated the population of CD11b + CD103 - DCs subsets in lungs of asthmatic mice and modulated the immune activation functions of DCs through NF-κB signaling pathway. The mixed lymphocyte response assay revealed that DCs mediated the suppressive effect of CC10 on Th2 cell responses. Collectively, CC10 profoundly mitigates Th2-type allergic inflammation in asthma by modulating lung DC phenotype and functions, highlighting its therapeutic potential for inflammatory airway conditions and other related immunological disorders., (© 2024. The Author(s).)

Objectives: To explore the diagnostic efficacy of serum 14-3-3β protein combined with fractional exhaled nitric oxide (FeNO) and conventional ventilatory lung function parameters in diagnosing bronchial asthma (referred to as "asthma") in children., Methods: A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group, and 85 healthy children undergoing routine health checks as the control group. The study compared the differences in serum 14-3-3β protein concentrations between the two groups, analyzed the correlation of serum 14-3-3β protein with clinical indices, and evaluated the diagnostic efficacy of combining 14-3-3β protein, FeNO, and conventional ventilatory lung function parameters for asthma in children., Results: The concentration of serum 14-3-3β protein was higher in the asthma group than in the control group ( P <0.001). Serum 14-3-3β protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E, and a negative correlation with conventional ventilatory lung function parameters ( P <0.05). Cross-validation of combined indices showed that the combination of 14-3-3β protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume had an area under the curve of 0.948 for predicting asthma, with a sensitivity and specificity of 88.9% and 93.7%, respectively, demonstrating good diagnostic efficacy ( P <0.001). The model had the best extrapolation., Conclusions: The combination of serum 14-3-3β protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume can significantly improve the diagnostic efficacy for asthma in children. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 723-729 .

Background: The dosage of ovalbumin (OVA) during the sensitization stage is considered a crucial factor in the development of airway hyperresponsiveness (AHR). However, the inconsistent dosages of sensitizing OVA used in current studies and the lack of research on their impact on AHR are notable limitations., Methods: We examined the impact of increasing sensitizing doses of OVA in a murine asthma model, which entailed initial sensitization with OVA followed by repeated exposure to OVA aerosols. BALB/c mice were primed with doses of OVA (0, 10, 20, 50, and 100 μg) plus 1 mg Alum on Days 0 and 7, and were challenged with OVA aerosols (10 mg/mL for 30 min) between Days 14 and 17. Antigen-induced AHR to methacholine (MCh), as well as histological changes, eosinophilic infiltration, and epithelial injury were assessed., Results: The result indicated that there are striking OVA dose-related differences in antigen-induced AHR to MCh. The most intense antigen-induced AHR to MCh was observed with sensitization at 50 μg, while weaker responses were seen at 10, 20, and 100 μg. Meanwhile, there was a significant increase in eosinophil count with sensitization at 50 μg. The changes of AHR were correlated with total cells count, lymphocytes count, eosinophils count, and basophils count in bronchoalveolar lavage fluid; however, it did not correlate with histological changes such as cellular infiltration into bronchovascular bundles and goblet cell hyperplasia of the bronchial epithelium., Conclusion: Overall, this study demonstrated that sensitization with 50 μg of OVA resulted in the most significant AHR compared to other dosages. These findings may offer valuable insights for future research on mouse asthma modeling protocols., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Chronic obstructive pulmonary disease (COPD) is the most common chronic airway disease, with a high prevalence and high disease burden. Clinical questions have driven advances in clinical research that continue to deepen our understanding of COPD. At the same time, new perspectives, evidence, and strategies have emerged. Studies since 2022 have increased knowledge of the impact of risk factors, such as low-to-moderate income and ambient ozone, on the prevalence of COPD. The effect of preterm birth on obstructive lung function deficits and COPD in the sixth decade of life was investigated for the first time. Screening studies for COPD in developed and low- and middle-income countries suggest the importance of tailoring screening strategies to local conditions. Developments in artificial intelligence provide a general framework for using machine-learning-based methods and medical record-based labels to improve disease prediction. New perspectives on endotypes/phenotypes and prognostic assessment of COPD were provided by lifetime spirometry patterns of obstruction and limitation, sensitisation to recombinant Aspergillus fumigatus allergens, airway-occluding mucus plugs and exacerbation history in COPD group A and B patients. Clinical trials focusing on inflammatory mediators, comorbidity treatment, non-pharmacological treatments, and environmental interventions shed light on some crucial and long-debated issues. Further research is needed for individualised diagnosis and treatment of COPD.

Asthma is a complex and heterogeneous respiratory disease that causes serious social and economic burdens. Current drugs such as β 2 -agonists cannot fully control asthma. Our previous study found that Transgelin-2 is a potential target for treating asthmatic pulmonary resistance. Herein, we discovered a zolinium compound, TSG1180, that showed a strong interaction with Transgelin-2. The equilibrium dissociation constants (KD) of TSG1180 to Transgelin-2 were determined to be 5.363 × 10 -6 and 9.81 × 10 -6 M by surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Cellular thermal shift assay (CETSA) results showed that the thermal stability of Transgelin-2 increased after coincubation of TSG1180 with lysates of airway smooth muscle cells (ASMCs). Molecular docking showed that Arg39 may be the key residue for the binding. Then, the SPR result showed that the binding affinity of TSG1180 to Transgelin-2 mutant (R39E) was decreased by 1.69-fold. Real time cell analysis (RTCA) showed that TSG1180 treatment could relax ASMCs by 19 % (P < 0.05). Once Transgelin-2 was inhibited, TSG1180 cannot induce a relaxation effect, suggesting that the relaxation effect was specifically mediated by Transgelin-2. In vivo study showed TSG1180 effectively reduced pulmonary resistance by 64 % in methacholine-induced mice model (P < 0.05). Furthermore, the phosphorylation of Ezrin at T567 was increased by 8.06-fold, the phosphorylation of ROCK at Y722 was reduced by 38 % and the phosphorylation of RhoA at S188 was increased by 52 % after TSG1180 treatment. These results suggested that TSG1180 could be a Transgelin-2 agonist for further optimization and development as an anti-asthma drug., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Asthma is a highly prevalent respiratory disease that remains difficult to control. Acupuncture, as an important alternative therapeutic modality in preventing and treating asthma, is widely used in the world due to its promising efficacy and safety. Although acupoint selection and combinations are critical to therapeutic effects of acupuncture, its fundamental rules for asthma have not been fully understood. Thus, using data mining, the present study aimed to discover the most effective acupoints and combinations in the acupuncture treatment of asthma., Methods: Controlled clinical trials (CCTs) of acupuncture treatment for asthma were searched and retrieved from databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang, and PubMed. Data regarding the main acupoints prescribed in these clinical trials was collected and quantified. A network analysis was performed to uncover the interconnections between the acupoints. Additionally, hierarchical clustering analysis and association rule mining were conducted to discover the potential acupoint combinations., Results: A total of 183 CCTs were retrieved. Feishu (BL13), Dingchuan (EX-B1), Dazhui (GV14), Shengshu (BL23), Pishu (BL20), and Fengmen (BL12) appeared to be the most frequently used acupoints for asthma. While the Bladder Meridian of Foot Taiyang, the Governor Vessel, and the Conception Vessel, compared to other meridians, were found to be the more commonly selected meridians. In the acupoint interconnection network, Feishu (BL13), Fengmen (BL12), Dingchuan (EX-B1), and Dazhui (GV14) were defined as key node acupoints. Moreover, acupoint clustering analysis revealed the treatment principle of "facilitating the flow of the lung Qi, tonifying spleen and kidney, and treating both the symptoms and root causes." Association rule mining analysis demonstrated that the combination of Pishu, Shenshu, Feishu, and Dingchuan, as well as that of Feishu, Dazhui, and Fengmen were potential acupoint combinations that should be selected with priority in asthma treatment., Conclusion: Based on a data mining analysis of published CCTs, this study provides valuable information regarding the selection of the most effective acupoints and combinations for clinical acupuncture practice and experimental study aimed at the prevention and treatment of asthma., (© 2021 S. Karger AG, Basel.)

A high platform can fix rats without restriction and completely expose the acupoints on the back during acupuncture manipulation. This article describes methods for the fabrication of the high platform, establishes a rat model of asthma and measures changes in respiratory function using a noninvasive and real-time whole-body plethysmography (WBP) system.

Ethnopharmacological Relevance: Standard therapy for asthma, a highly heterogeneous disease, is primarily based on bronchodilators and immunosuppressive drugs, which confer short-term symptomatic relief but not a cure. It is difficult to discover novel bronchodilators, although potential new targets are emerging. Traditional Chinese Medicine (TCM) formulas have been used to treat asthma for more than 2000 years, forming the basis for representative asthma treatments., Aim of the Study: Based on the efficacy of TCM formulas, anti-asthmatic herbal compounds bind proteins are potential targets for asthma therapy. This analysis will provide new drug targets and discovery strategies for asthma therapy., Materials and Methods: A list of candidate herbs for asthma was selected from the classical formulas (CFs) of TCM for the treatment of wheezing or dyspnea recorded in Treatise on Cold Damage and Miscellaneous Diseases (TCDMD) and from modern herbal formulas identified in the SAPHRON TCM Database using the keywords "wheezing" or "dyspnea". Compounds in the selected herbs and compounds that directly bind target proteins were acquired by searching the Herbal Ingredients' Targets Database (HITD), TCM Data Bank (TCMDB) and TCM Integrated Database (TCMID). Therapeutic targets of conventional medicine (CM) for asthma were collected by searching Therapeutic Target Database (TTD), DrugBank and PubMed as supplements. Finally, the enriched gene ontology (GO) terms of the targets were obtained using the Database for Annotation Visualization and Integrated Discovery (DAVID) and protein-protein interactions (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The effects of two selected TCM compounds, kaempferol and ginkgolide A, on cellular resistance in human airway smooth muscle cells (ASMCs) and pulmonary resistance in a mouse model were investigated., Results: The list of 32 candidate herbs for asthma was selected from 10 CFs for the treatment of wheezing or dyspnea recorded in TCDMD and 1037 modern herbal formulas obtained from the SAPHRON TCM Database. A total of 130 compounds from the 32 selected herbs and 68 herbal compounds directly bind target proteins were acquired from HITD and TCMDB. Eighty-eight therapeutic targets of CM for asthma were collected by searching TTD and PubMed as supplements. DAVID and STRING analyses showed targets of TCM formulas are primarily related to cytochrome P450 (CYP) family, transient receptor potential (TRP) channels, matrix metalloproteinases (MMPs) and ribosomal protein. Both TCM formulas and CM act on the same types of targets or signaling pathways, such as G protein-coupled receptors (GPCRs), steroid hormone receptors (SHRs), and JAK-STAT signaling pathway. The proteins directly targeted by herbal compounds, TRPM8, TRPA1, TRPV3, CYP1B1, CYP2B6, CYP1A2, CYP3A4, CYP1A1, PPARA, PPARD, NR1I2, MMP1, MMP2, ESR1, ESR2, RPLP0, RPLP1 and RPLP2, are potential targets for asthma therapy. In vitro results showed kaempferol (1 × 10 -2  mM) and ginkgolide A (1 × 10 -5  mM) significantly increased the cell index (P < 0.05 vs. histamine, n = 3) and therefore relaxed human ASMCs. In vivo results showed kaempferol (145 μg/kg) and ginkgolide A (205 μg/kg) significantly reduced pulmonary resistance (P < 0.05 vs. methacholine, n = 6)., Conclusion: Potential target discovery for asthma treatment based on the clinical effectiveness of TCM is a feasible strategy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Acupuncture has long been used for asthma treatment but the underlying mechanism remains unclear. Previous study showed that metallothionein-2 (MT-2) was significantly decreased in asthmatic lung tissue. However, the relationship between acupuncture treatment and MT-2 expression during asthma is still unknown, and the detailed effect analysis of MT-2 on phosphorylation in airway smooth muscle cells (ASMCs) is also unclear., Methods: The acupuncture effect on pulmonary resistance (RL) was investigated in a rat model of asthma, and the mRNA and protein levels of MT-2 in lung tissue were detected. Primary ASMCs were isolated and treated with MT-2 recombinant protein to study the MT-2 effects on ASMC relaxation. A Phospho Explorer antibody microarray was applied to detect protein phosphorylation changes associated with MT-2-induced ASMC relaxation. Bioinformatic analysis were performed with PANTHER database, DAVID and STRING. Phosphorylation changes in key proteins were confirmed by Western blot., Results: Acupuncture significantly reduced RL at 2-5 min (P < 0.05 vs asthma) in asthmatic rats. Acupuncture continued to increase MT-2 mRNA expression in lung tissue for up to 14 days (P < 0.05 vs asthma). The MT-2 protein expression was significantly decreased in the asthmatic rats (P < 0.05 vs control), while MT-2 protein expression was significantly increased in the asthmatic model group treated with acupuncture (P < 0.05 vs asthma). Primary ASMCs were successfully isolated and recombinant MT-2 protein (100, 200, 400 ng/ml) significantly relaxed ASMCs (P < 0.05 vs control). MT-2 induced phosphorylation changes in 51 proteins. Phosphorylation of 14 proteins were upregulated while 37 proteins were downregulated. PANTHER classification revealed eleven functional groups, and the phosphorylated proteins were identified as transferases (27.8 %), calcium-binding proteins (11.1 %), etc. DAVID functional classification showed that the phosphorylated proteins could be attributed to eight functions, including protein phosphorylation and regulation of GTPase activity. STRING protein-protein interaction network analysis showed that Akt1 was one of the most important hubs for the phosphorylated proteins. The phosphorylation changes of Akt1 and CaMK2β were consistent in both the Phospho Explorer antibody microarray and Western blot., Conclusion: Acupuncture can significantly ameliorate RL, and the MT-2 mRNA and protein levels in lung tissue are increased during treatment. MT-2 significantly relaxes ASMCs and induces a series of protein phosphorylation. These phosphorylation changes, including Akt1 and CaMK2β, may play important roles in the therapeutic effects of acupuncture on asthma., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Transgelin-2 has been regarded as an actin-binding protein that induces actin gelation and regulates actin cytoskeleton. However, transgelin-2 has recently been shown to relax the myosin cytoskeleton of the airway smooth muscle cells by acting as a receptor for extracellular metallothionein-2. From a clinical perspective, these results support transgelin-2 as a promising therapeutic target for diseases such as cancer and asthma. The inhibition of transgelin-2 prevents actin gelation and thereby cancer cell proliferation, invasion, and metastasis. Conversely, the activation of transgelin-2 with specific agonists relaxes airway smooth muscles and reduces pulmonary resistance in asthma. Here, we review new studies on the biochemical properties of transgelin-2 and discuss their clinical implications for the treatment of immune, oncogenic, and respiratory disorders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

There is a clinical need for new bronchodilator drugs in asthma, because more than half of asthmatic patients do not receive adequate control with current available treatments. We report that inhibition of metallothionein-2 protein expression in lung tissues causes the increase of pulmonary resistance. Conversely, metallothionein-2 protein is more effective than β 2 -agonists in reducing pulmonary resistance in rodent asthma models, alleviating tension in tracheal spirals, and relaxing airway smooth muscle cells (ASMCs). Metallothionein-2 relaxes ASMCs via transgelin-2 (TG2) and induces dephosphorylation of myosin phosphatase target subunit 1 (MYPT1). We identify TSG12 as a nontoxic, specific TG2-agonist that relaxes ASMCs and reduces asthmatic pulmonary resistance. In vivo, TSG12 reduces pulmonary resistance in both ovalbumin- and house dust mite-induced asthma in mice. TSG12 induces RhoA phosphorylation, thereby inactivating the RhoA-ROCK-MYPT1-MLC pathway and causing ASMCs relaxation. TSG12 is more effective than β 2 -agonists in relaxing human ASMCs and pulmonary resistance with potential clinical advantages. These results suggest that TSG12 could be a promising therapeutic approach for treating asthma., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: There is some evidence to support the use of acupuncture as an alternative therapy for asthma. However, the mechanisms underlying its effects are not fully understood. We have reported previously that acupuncture has beneficial effects on asthma without changing the concentration of serum cortisol, although endogenous glucocorticoid (GC) plays an important role in regulating immune responses., Objective: In this study, bilateral adrenalectomy (removal of both adrenal glands) was performed in rats before asthma model induction to investigate whether acupuncture influences asthma in a GC-dependent manner., Methods: Adrenal-intact and adrenalectomised rats were injected with ovalbumin to induce asthma and then left untreated or treated with manual acupuncture (MA) at GV14, bilateral BL12 and bilateral BL13, or manual restraint without MA. Healthy and sham-adrenalectomised control groups were also included. Pulmonary resistance (R L ), serum concentrations of corticosterone, and eosinophil counts were measured at the end of the experimental course. Sera from adrenal-intact and adrenalectomised asthmatic rats treated with acupuncture were injected into untreated adrenal-intact and adrenalectomised asthmatic rats to investigate further the potential role of GC in the effect of acupuncture., Results: Acupuncture significantly decreased R L and eosinophil count in both adrenal-intact and adrenalectomised asthmatic rats. Moreover, administration of sera derived from acupuncture-treated adrenal-intact and adrenalectomised asthmatic rats attenuated the increase in R L and eosinophil count in both asthmatic models., Conclusions: Results of this study suggest that endogenous GC is not a key contributor to the effects of acupuncture on asthma, and that acupuncture may have potentially therapeutic effects on asthma in a GC-independent manner., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background . Asthma is a disease with a core abnormality in airway smooth muscle function, and the proliferation of airway smooth muscle cells (ASMCs) plays a pivotal role in asthma airway remodeling. Our previous study showed that S100A9 (S100 calcium-binding protein A9; 400 and 800 ng/mL) significantly inhibited rat ASMCs proliferation at 48 h, and 50-800 ng/mL S100A9 (50, 100, 200, 400, and 800 ng/mL) also induced a lasting effect by significantly inhibiting rat ASMCs proliferation at 72 h in a dose-dependent manner. However, the intracellular effects of S100A9 on ASMCs proliferation remain unknown. Methods . Rat ASMCs with stable S100A9 knockdown were generated using short hairpin RNA. The effects of decreased S100A9 expression on cellular proliferation, the production of reactive oxygen species (ROS), and p38 MAPK pathway protein expression were examined. Results . Decreased intracellular S100A9 expression significantly promoted platelet-derived growth factor-induced rat ASMCs proliferation and increased ROS production. The antioxidative agent N-acetylcysteine significantly inhibited rat ASMCs proliferation. Western blot results showed that the decreased intracellular S100A9 expression significantly inhibited p38 MAPK phosphorylation. Conclusion . Decreased S100A9 expression promoted rat ASMCs proliferation by stimulating ROS generation and inhibiting p38 MAPK. Our study may provide novel insights into the regulation of asthma airway remodeling., Competing Interests: The authors declare that they have no competing interests.

Background: Although asthma symptoms can be temporarily controlled, it is recommended to use effective low-risk, non-drug strategies to constitute a significant advance in asthma management. Acupuncture has been traditionally used to treat asthma; however, the evidence for the efficacy of this treatment is still lacking. Previous clinical trials of acupuncture in treating asthma were limited by methodological defects; therefore, high-quality research is required., Methods/design: This trial is designed as a multi-center, randomized, double-blind, parallel-group controlled trial. Patients with mild to moderate asthma will be randomly allocated to either a verum acupuncture plus as-needed salbutamol aerosol and/or prednisone tablets group or a sham acupuncture plus as-needed salbutamol aerosol and/or prednisone tablets group. Acupoints used in the verum acupuncture group are GV14 (Da Zhui), BL12 (Feng Men), BL13 (Fei Shu) and acupoints used in the sham acupuncture group are DU08 (Jin Suo), BL18 (Gan Shu), BL19 (Dan Shu). After a baseline period of 1 week, the patients in both groups will receive verum/sham acupuncture once every other day with a total of 20 treatment sessions in 6 weeks and a 3-month follow-up. The primary outcome will be measured by using the asthma control test and the secondary outcomes will be measured by using the percentage of symptom-free days, the average dosage of salbutamol aerosol and/or prednisone tablets, lung functions, daily asthma symptom scores, asthma quality of life questionnaire, and so on., Discussion: This trial will assess the effect of acupuncture on asthma and aims to provide reliable clinical evidence for the efficacy of acupuncture in treating asthma., Trial Registration: ClinicalTrials.gov Identifier: NCT01931696 , registered on 26 August 2013.

This study examines the clinical and immunomodulatory effects of acupuncture in the treatment of patients with allergic asthma. The acupuncture points GV14, BL12, and BL13 were selected based on the theory of traditional Chinese medicine in treating asthma. Manual acupuncture was performed once every other day (three times per week) for 5 weeks. The needles were twisted approximately 360° evenly at the rate of 60 times/min for 20 s, manipulated every 10 min and withdrawn after 30 min. Concentrations of sIgA and total IgA in secretions were determined by the combination of sucrose density gradient ultracentrifugation and RIA. Levels of cortisol in the plasma were measured by RIA. Total IgE in the sera was examined by ELISA. Flow cytometry was used to detect the numbers of CD3+, CD4+, CD8+, and IL-2R + T lymphocytes in the peripheral blood. The absolute and differential numbers of eosinophils in peripheral blood were counted with eosin staining. The total efficacy of the acupuncture treatment in patients with allergic asthma at the end of one course of treatment was 85 %. After treatment, the concentrations of sIgA and total IgA in the saliva (P<0.01, P<0.02) and nasal secretions (P<0.02, P<0.02) were significantly decreased in patients with allergic asthma. The levels of total IgE in sera (P<0.001), the counts of IL-2R + T lymphocytes (P<0.001), and the absolute and differential numbers of eosinophils (P<0.01, P<0.01) in the peripheral blood were also significantly decreased. The numbers of CD3+, CD4+, and CD8+ T lymphocytes in the peripheral blood were significantly increased in the allergic asthmatics treated by acupuncture (P<0.001, P<0.01, and P<0.001, respectively). The concentration of cortisol in the plasma of asthmatic patients did not change significantly after the acupuncture treatment (P>0.05). Acupuncture has regulatory effects on mucosal and cellular immunity in patients with allergic asthma and may be an adjunctive therapy for allergic asthma.

S100A8, an important member of the S100 protein family, is a low-molecular-weight (10.8 kDa) calcium-binding protein containing conserved EF-hand structural motifs. Previous studies have shown that the biological function of S100A8 protein is associated with a variety of inflammatory diseases, for example asthma. S100A8 protein plays important roles in the regulation of inflammation. It can activate inflammatory cells and cytokines via chemotactic activity for neutrophils, and bind to the receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4), thus mediating intracellular inflammatory signaling transduction. Additionally, recent studies have reported the anti-inflammation activity of S100A8 protein, which indicates that S100A8 may have a more complex function of biological regulation in the different pathophysiological conditions. In this review, we summarized the studies on the functions and molecular mechanisms of S100A8 protein in inflammation, which would propose a novel strategy for the prophylaxis and treatment of asthma and other inflammatory diseases.

Background: The inhalation of allergens by allergic asthmatics results in the early asthmatic response (EAR), which is characterized by acute airway obstruction beginning within a few minutes. The EAR is the earliest indicator of the pathological progression of allergic asthma. Because the molecular mechanism underlying the EAR is not fully defined, this study will contribute to a better understanding of asthma., Methods: In order to gain insight into the molecular basis of the EAR, we examined changes in protein expression patterns in the lung tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques. Bioinformatic analysis of the proteomic data was then performed using PPI Spider and KEGG Spider to investigate the underlying molecular mechanism., Results: In total, 44 differentially expressed protein spots were detected in the 2-DE gels. Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully identified using mass spectrometry. During subsequent bioinformatic analysis, the gene ontology classification, the protein-protein interaction networking and the biological pathway exploration demonstrated that the identified proteins were mainly involved in glycolysis, calcium binding and mitochondrial activity. Using western blot and semi-quantitative RT-PCR, we confirmed the changes in expression of five selected proteins, which further supports our proteomic and bioinformatic analyses., Conclusions: Our results reveal that the allergen-induced EAR in asthmatic rats is associated with glycolysis, calcium binding and mitochondrial activity, which could establish a functional network in which calcium binding may play a central role in promoting the progression of asthma.

S100A9 is a member of the S100 family of proteins that contain two EF-hand calcium-binding motifs. We previously reported that S100A9 was differentially expressed during the early airway response phase of asthma and can be regulated by acupuncture. To understand the possible role of S100A9 in asthma, the effects of the S100A9 were investigated in a rat model of asthma and in isolated tracheal spirals. The pulmonary function and isometric tension were measured after the administration of purified recombinant S100A9. The results of in vivo experiments showed that S100A9 (0.1microg/kg) significantly decreased the pulmonary resistance and increased the dynamic compliance. The in vitro experimental results showed that S100A9 (100, 200, 400, or 800ng/ml, final concentrations) significantly reduced the isometric tension of isolated tracheal spirals. These results suggest that S100A9 elicits dose-dependent anti-asthmatic effects and may provide further insight into the treatment of asthma., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Asthma has become an important public health issue and approximately 300 million people have suffered from the disease worldwide. Nowadays, the use of acupuncture in asthma is increasing. This study intended to systematically analyze and compare the gene expression profiles between the asthmatic and acupuncture-treated asthmatic rat lung, and tried to gain insight into the molecular mechanism underlying the early airway response (EAR) phase of asthma treated by acupuncture., Methods: Four tag libraries of serial analysis of gene expression (SAGE) were established from lung tissues of control rats (CK), asthmatic rats (AS), asthmatic rats treated by acupuncture (ASAC), and control rats treated by acupuncture (CKAC). Bioinformatic analyses were carried out by using the methods including unsupervised hierarchical clustering, functional annotation tool of the database for annotation, visualization, and integrated discovery (DAVID), gene ontology (GO) tree machine, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis., Results: There were totally 186 differentially expressed tags (P < 0.05, P(CK/AS)) between the libraries of CK and AS, 130 differentially expressed tags between libraries of AS/ASAC (P < 0.05, P(AS/ASAC)), and 144 differentially expressed tags between libraries of CK/CKAC (P < 0.05, P(CK/CKAC)). The gene expression profiles of AS and ASAC were more similar than other libraries via unsupervised SAGE clustering. By comparison of P(CK/AS) and P(AS/ASAC), the DAVID genes functional classification was found to be changed from "immune response" to "response to steroid hormone stimulus", and the GO term "antigen processing and presentation of peptide antigen" disappeared in P(AS/ASAC). Totally 3 same KEGG pathways were found among the three groups. Moreover, 21 specific tags of the acupuncture in treating asthma were detected using Venn diagrams., Conclusion: Our SAGE research indicates that the gene expression profile of the EAR phase of asthma could be effectively and specifically regulated by acupuncture, which suggests that the gene expression of immune response and steroid hormone may play an important role in the treatment.

Background and Objective: The pathogenesis and molecular mechanism underlying asthma remain undetermined. The purpose of this study was to identify genes and pathways involved in the early airway response (EAR) phase of asthma by using serial analysis of gene expression (SAGE)., Methods: Two SAGE tag libraries of lung tissues derived from a rat model of asthma and controls were generated. Bioinformatic analyses were carried out using the Database for Annotation, Visualization and IntegratedDiscovery Functional Annotation Tool, Gene Ontology (GO) TreeMachine and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis., Results: A total of 26 552 SAGE tags of asthmatic rat lung were obtained, of which 12 221 were unique tags. Of the unique tags, 55.5% were matched with known genes. By comparison of the two libraries, 186 differentially expressed tags (P < 0.05) were identified, of which 103 were upregulated and 83 were downregulated. Using the bioinformatic tools these genes were classified into 23 functional groups, 15 KEGG pathways and 37 enriched GO categories., Conclusions: The bioinformatic analyses of gene distribution, enriched categories and the involvement of specific pathways in the SAGE libraries have provided information on regulatory networks of the EAR phase of asthma. Analyses of the regulated genes of interest may inform new hypotheses, increase our understanding of the disease and provide a foundation for future research.

Cai-Tao Chen,1 Chun-Xiao Shan,2 Jun Ran,3 Lei-Miao Yin,1 Hai-Yan Li,4 Yu Wang,1 Yu-Dong Xu,1 Jing-Lei Guo,5 Yang-Lin Shi,1 Yan-Jiao Chen,1 Yong-Qing Yang1 1Shanghai Research Institute of Acupuncture and Meridian, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China; 3Chongqing Hospital of Traditional Chinese Medicine, Chongqing, People’s Republic of China; 4Shanghai First Rehabilitation Hospital, Shanghai, People’s Republic of China; 5School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Yong-Qing Yang; Yan-Jiao ChenLaboratory of Molecular Biology, Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, 650 South Wanping Road, Shanghai, 200030, People’s Republic of ChinaTel +86-21-54592134; +86-21-64395975Fax +86-21-64395975Email yyq@shutcm.edu.cn; cyjb1018@163.comPurpose: Cyclophilin A (CypA) inhibits CD4+ T cell signal transduction via interleukin-2-inducible T-cell kinase (Itk), a tyrosine kinase required for T helper (Th) 2 cells function. Furthermore, mice with CypA silencing developed allergic diseases associated with increased Th2 cytokines production. CD4+ T cells with a Th2-cytokine pattern have been demonstrated to have a pivotal role in the pathogenesis of asthma. However, the effects of CypA in regulating immunity in asthma and in relieving asthmatic symptoms in vivo are entirely unknown.Methods: Recombinant CypA protein (rCypA) was generated and purified. Ovalbumin (OVA)-challenged asthmatic rats model and acetylcholine chloride (ACh)-induced contraction of tracheal spirals were established. The pulmonary resistance (RL) value of asthmatic rats in vivo and the isometric tension of tracheal spirals ex vivo were recorded by MFLab 3.01 software. The levels of Th1 and Th2 cytokines and the quantities of immunoglobulin (IgA, IgG, IgM and IgE) in the supernatants of rat spleen lymphocytes were detected and analysed by bio-plex Suspension Array System and ELISA, respectively. CD4+ T cells were separated by MicroBeads, and the levels of interleukin (IL)-4 and interferon-γ (IFN-γ) were detected by ELISA.Results: rCypA (10 ng/kg) significantly reduced RL within 2– 7 min in OVA-challenged asthmatic rats in vivo, and there were no significant differences compared with terbutaline (TB) and hydrocortisone (HC). Furthermore, rCypA (10 ng/mL) significantly reduced the isometric tension in the ACh-induced contraction of the tracheal spiral ex vivo, and the effect of rCypA was better than that of TB. Additionally, rCypA suppressed the secretion of both Th1 and Th2 cytokines, and the suppressive effects of rCypA were stronger than those of HC, especially on Th2 cytokines.Conclusion: These findings indicate that CypA may serve as a potential novel therapeutic strategy for asthma.Keywords: cyclophilin A, asthma, Th2 cytokines, immunoregulation