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This article discusses a study that examines the potential use of soluble programmed death 1 (sPD-1) as a biomarker for predicting mortality in patients with adult-onset Still's disease (AOSD). AOSD is a systemic inflammatory disease with a varied clinical course, and currently, there are no established biomarkers for predicting prognosis. The study included 69 patients with AOSD and found that higher levels of sPD-1 were associated with worse survival outcomes. The authors suggest that sPD-1 could be a valuable indicator for mortality in patients with AOSD. However, further research is needed to confirm the usefulness of sPD-1 levels as an indicator of diagnosis and disease activity in AOSD patients. [Extracted from the article]

Author(s): Je-Min Choi [1]; Mi-Hyun Ahn [2]; Wook-Jin Chae [1]; Yung-Gook Jung [1]; Jae-Chul Park [1]; Hyun-Mi Song [2]; Young-Eun Kim [2]; Jung-Ah Shin [2]; Choon-Sik Park [2]; Jung-Won Park [...]

Abstract Background Interleukin-8 (IL-8) is a potent chemo-attractant cytokine responsible for neutrophil infiltration in lungs with idiopathic pulmonary fibrosis (IPF). The IL-8 protein and mRNA expression are increased in the lung with IPF. We evaluated the effect of single nucleotide polymorphisms (SNPs) of the IL-8 gene on the risk of IPF. Methods One promoter (rs4073T>A) and two intronic SNPs (rs2227307T>G and rs2227306C>T) of the IL-8 genes were genotyped in 237 subjects with IPF and 456 normal controls. Logistic regression analysis was applied to evaluate the association of these SNPs with IPF. IL-8 in BAL fluids was measured using a quantitative sandwich enzyme immunoassay, and promoter activity was assessed using the luciferase reporter assay. Results The minor allele frequencies of rs4073T>A and rs2227307T>G were significantly lower in the 162 subjects with surgical biopsy-proven IPF and 75 subjects with clinical IPF compared with normal controls in the recessive model (OR = 0.46 and 0.48, p = 0.006 and 0.007, respectively). The IL-8 protein concentration in BAL fluids significantly increased in 24 subjects with IPF compared with 14 controls (p = 0.009). Nine IPF subjects homozygous for the rs4073 T>A common allele exhibited higher levels of the IL-8 protein compared with six subjects homozygous for the minor allele (p = 0.024). The luciferase activity of the rs4073T>A common allele was significantly higher than that of the rs4073T>A minor allele (p = 0.002). Conclusion The common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.

Abstract Background Inhalation of particles aggravates respiratory symptoms including mucus hypersecretion in patients with chronic airway disease and induces goblet cell hyperplasia (GCH) in experimental animal models. However, the underlying mechanisms remain poorly understood. Methods To understand this, the numbers of goblet cells, Muc5ac (+) expressing epithelial cells and IL-13 expressing mast cells were measured in the trachea of sham or TiO2 particles – treated rats using periodic acid-Schiff, toluidine blue and immunohistochemical staining. RT-PCR for Muc-1, 2 and 5ac gene transcripts was done using RNA extracted from the trachea. Differential cell count and IL-13 levels were measured in bronchoalveolar lavage (BAL) fluid. In pretreatment groups, cyclophosphamide (CPA) or dexamethasone (DEX) was given before instillation of TiO2. TiO2 treatment markedly increased Muc5ac mRNA expression, and Muc5ac (+) or PAS (+) epithelial cells 48 h following treatment. Results The concentration of IL-13 in BAL fluids was higher in TiO2 treated – rats when compared to those in sham rats (p < 0.05). Pretreatment with cyclophosphamide (CPA) decreased the number of neutrophils and eosinophils in BAL fluid of TiO2 treated – rats (p < 0.05), but affected neither the percentage of PAS (+) cells, nor IL-13 levels in the BAL fluids (p > 0.05). In contrast, pretreatment with dexamethasone (DEX) diminished the percentage of PAS (+) cells and the levels of IL-13 (p < 0.05). TiO2 treatment increased the IL-13 (+) mast cells (p < 0.05) in the trachea, which was suppressed by DEX (p < 0.05), but not by CPA pretreatment (p > 0.05). In addition there were significant correlations of IL-13 (+) rate of mast cells in the trachea with IL-13 concentration in BAL fluid (p < 0.01) and with the percentage of Muc5ac (+) cells in the sham and TiO2 treated rats (p < 0.05). Conclusion In conclusion, TiO2 instillation induces GCH and Muc5ac expression, and this process may be associated with increased production of IL-13 by mast cells.

Objectives: This study evaluated the SDF-1/CXCL12 and soluble CXCR4 (sCXCR4) levels, and investigated their clinical relevance in adult-onset Still's disease (AOSD)., Methods: Forty-two AOSD patients and 30 healthy controls (HC) were enrolled for serum sampling. Expression levels of CXCL12 and CXCR4 in skin biopsy materials of 40 AOSD patients, 10 patients with eczema, or 10 psoriasis, and 10 HC skin were evaluated with immunohistochemistry., Results: The serum CXCL12 levels in patients with AOSD (2,452±1,531 pg/mL) were higher than those in HC (1,708±1,322 pg/mL, p=0.017). The serum sCXCR4 levels in patients with AOSD (14,449±16,627 pg/mL) were higher than those in HC (3,046±2,554 pg/mL, p<0.001). Serum CXCL12 levels correlated positively with counts of leukocytes and neutrophils, erythrocyte sedimentation rate, ferritin, and C-reactive protein (CRP). Serum sCXCR4 levels correlated positively with systemic scores, platelet counts, and CRP levels. The serum levels of CXCL12 and sCXCR4 were decreased significantly in the patients with AOSD followed after resolution of disease activity. On immunohistochemical stain, the mean percentage of CXCR4-positive inflammatory cells was 51.4±27.5% and that of CXCL12-positive inflammatory cells was 16.7±13.3% in AOSD patients. CXCR4 was more frequently expressed in inflammatory cells from AOSD patients than in those with eczema or psoriasis and HC skin., Conclusions: These results provide that sCXCR4 could be a clinical biomarker of evaluation for disease activity in AOSD, and show that CXCR4/CXCL12 may influence the inflammatory condition and skin manifestations of AOSD.

Many therapeutic glycoproteins have been successfully generated in plants. Plants have advantages regarding practical and economic concerns, and safety of protein production over other existing systems. However, plants are not ideal expression systems for the production of biopharmaceutical proteins, due to the fact that they are incapable of the authentic human N-glycosylation process. The majority of therapeutic proteins are glycoproteins which harbor N-glycans, which are often essential for their stability, folding, and biological activity. Thus, several glyco-engineering strategies have emerged for the tailor-making of N-glycosylation in plants, including glycoprotein subcellular targeting, the inhibition of plant specific glycosyltranferases, or the addition of human specific glycosyltransferases. This article focuses on plant N-glycosylation structure, glycosylation variation in plant cell, plant expression system of glycoproteins, and impact of glycosylation on immunological function. Furthermore, plant glyco-engineering techniques currently being developed to overcome the limitations of plant expression systems in the production of therapeutic glycoproteins will be discussed in this review.

In a search for new molecular pathways associated with asthma, we performed an mRNA differential display analysis using total RNA extracted from the tracheal tissues of ovalbumin (OVA)-challenged mice and sham controls. cDNAs corresponding to mRNAs for which expression levels were altered by OVA-challenge were isolate and sequenced. Twenty-eight genes differentially expressed in sham and OVA challenged mice were identified. A GenBank BLAST homology search revealed that they were related to cytoskeleton remodeling, transcription, protein synthesis and modification, energy production, and cell growth and differentiation. Two were selected for further characterization. Up-regulation of both the perinatal skeletal myosin heavy chain (skMHC) and fast skeletal muscle myosin light chain (skMLC) genes was confirmed by RT-PCR of trachea tissue from OVA challenged mice. Overexpression of skMLC protein was observed in the smooth muscle layers of OVA-challenged mice by immunohistochemistry, and the surface areas stained with skMLC antibody increased in the OVA-challenged mice. The overexpression of skMLC in murine asthma may be associated with the changes of bronchial smooth muscle.

Regulatory T cells, which stimulate or inhibit the effector functions of distinct T cell subsets, are critical in the control of the immune response. We investigated the effect of TGF-beta and IL-10 on T cell subsets according to the Th1/Th2 immune status. Sixty-two patients with asthma and 38 patients with pulmonary tuberculosis were included. Allergy skin tests, tuberculin tests, and chest radiography were performed. The levels of circulating IL-4, IFN-gamma, TGF-beta1, and IL-10 were measured using ELISA. The level of TGF-beta1 was higher in patients with asthma than in those with tuberculosis, but the IL-10 levels were the same between the asthma and tuberculosis groups. Atopy was unrelated to the tuberculin response. The IFN-gamma level was correlated with the IL-10 level, and the level of IL-4 was unrelated to the IL-10 or TGF-beta1 level. The level of IL-10 was higher in the negative tuberculin reactors than in the positive tuberculin reactors among patients with asthma, and TGF-beta1 was higher in the positive tuberculin reactors than in the negative tuberculin reactors among patients with tuberculosis. These results demonstrate that the regulatory effects of circulating TGF-beta and IL-10 on T cell cytokines may be different between Th2-type asthma and Th1 tuberculosis.