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IL-26 is a potentially important player in host defense and may be a pathogenic factor in the chronic inflammatory disorders of humans. However, the involvement of IL-26 in tuberculous pleural effusion (TPE) has not been investigated. The concentration of IL-26 was determined in pleural fluids and sera from patients with pleural effusions. Flow cytometry was performed to identify the cell origin of IL-26. The effects of tuberculosis-specific antigen (ESAT-6/CFP-10) on IL-26 expression of CD4+ T cell were explored. The impacts of IL-26 on modulating CD4+ T cell polarization were also investigated. The concentrations of IL-26 were much higher in tuberculous, malignant, and infectious PE than those in the corresponding serum. The expression of IL-26 on CD4+ T cells was much higher in tuberculous PE than those in the corresponding serum, and pleural Th1 and Th17 cells might be the major cell sources of IL-26. The addition of ESAT-6/CFP-10 to CD4+ T cells led to increasing the number of IL-26-producing CD4+ T cells and IL-26 expression on Th1 and Th17 cells. IL-26 could induce the differentiation and generation of IL-22 by memory and naive CD4+ T cells. IL-26 also upregulated the mRNA encoding CC-chemokine ligand 20 (CCL20) and CCL22 by mononuclear cells isolated from TPE. This study implies that pleural Th1 and Th17 cells are the major cell sources of IL-26, which could induce the differentiation and generation of Th22 cells by CD4+ T cells, suggesting the involvement of IL-26 in the pathogenesis of human TPE. KEY MESSAGES: IL-26 is overexpressed in TPE patients and presents a higher concentration in pleural effusion than the corresponding peripheral blood. Pleural Th1 and Th17 cells might be the major cell sources of IL-26 in TPE patients. IL-26 promotes IL-22 secretion and Th22 generation by CD4+ T cells isolated from TPE patients. IL-26 may play an active role in the pathogenesis of tuberculous pleurisy.

Background and objective Platelet activation, inflammatory reactions and oxidative stress are common pathogenesis of chronic obstructive pulmonary disease (COPD) with pulmonary heart disease (PHD). Mean platelet volume (MPV) and red blood cell distribution width (RDW) form part of the pathomechanisms of these conditions. Here, we investigated whether MPV and RDW can be biomarkers of PHD occurring secondary to COPD. Materials and methods This was a retrospective study on 229 participants with COPD. Among them, 69 had PHD. Complete blood count (CBC), blood gas analysis, pulmonary function tests and echocardiography were analyzed. Results MPV and RDW-standard deviation (RDW-SD) were significantly higher in patients with PHD than in patients without PHD (P ≤ 0.001). MPV and RDW-SD were positively correlated with pulmonary artery pressure (PAP) and the size of the right ventricle (P ≤ 0.05). Multivariate regression analysis showed that the risk of PHD increased 3-fold per unit rise in MPV (OR = 2.901, P ≤ 0.001). We observed that the risk of PHD increased 1.5 times per unit rise in RDW-SD (OR = 1.371, P ≤ 0.001).The AUC of ROC curve for the combined MPV and RDW-SD in predicting PHD among COPD patients was 0.900 (95％CI: 0.846-0．954, P ≤ 0.001), with a sensitivity of 76.8% and a specificity of 99.4%. Conclusions Both MPV and RDW-SD were significantly elevated and correlated with disease severity in COPD patients with PHD. A combination of these two parameters presents an effective biomarker of PHD.

The imbalance of CD4+Foxp3+ T cell subsets is reportedly involved in abnormal inflammatory immune responses in patients with chronic obstructive pulmonary disease (COPD). However, the possible role of CD4+CD25−Foxp3+ T cells in immune regulation in COPD remains to be investigated. In the current study, distribution and phenotypic characteristics of CD4+CD25−Foxp3+ T cells from peripheral blood were determined by flow cytometry; the origin, immune function and ultimate fate of CD4+CD25−Foxp3+ T cells were further explored in vitro. It was observed that circulating CD4+CD25−Foxp3+ T cells were significantly increased in stable COPD patients (SCOPD) and resembled central memory or effector memory T cells. Compared with peripheral CD4+CD25+Foxp3+ T cells, peripheral CD4+CD25−Foxp3+ T cells showed a lower expression of Foxp3, CTLA-4, HELIOS, and TIGIT, but a higher expression of CD127 and KI-67, suggesting that CD4+CD25−Foxp3+ T cells lost the expression of Tregs-associated molecules following the reduction in CD25. Unexpectedly, our study found that transforming growth factor-β1 (TGFβ1) decreased CD25 expression and played a critical role in the generation of CD4+CD25−Foxp3+ T cells from CD4+CD25+Foxp3+ T cells. Phenotypic analysis further revealed that both inducible and peripheral CD4+CD25−Foxp3+ T cells exhibited the features of activated conventional T cells. Importantly, memory CD4+CD25−Foxp3+ T cells facilitated the proliferation and differentiation of naïve CD4+ T cells into Th17 cells in the presence of IL-1β, IL-6, IL-23, and TGFβ1. Finally, a fraction of CD4+CD25−Foxp3+ T cells, exhibiting instability and plasticity, were converted to Th17 cells when subjected to Th17 cell-polarizing condition. Taken together, we propose that TGFβ1 is responsible for the generation of CD4+CD25−Foxp3+ T cells, and these cells functionally exert an auxiliary effect on Th17 cells generation and might perpetuate chronic inflammation in COPD.

IL-26 is a potentially important player in host defense and may be a pathogenic factor in the chronic inflammatory disorders of humans. However, the involvement of IL-26 in tuberculous pleural effusion (TPE) has not been investigated. The concentration of IL-26 was determined in pleural fluids and sera from patients with pleural effusions. Flow cytometry was performed to identify the cell origin of IL-26. The effects of tuberculosis-specific antigen (ESAT-6/CFP-10) on IL-26 expression of CD4

In CD4+ T helper (Th) cells, transforming growth factor β (TGF-β) is indispensable for the induction of both regulatory T (Treg) and interleukin-17-producing effector T helper (Th17) cells. Although BMP and activin membrane-bound inhibitor (BAMBI) is part of a rheostat-like mechanism for the regulation of TGF-β signalling and autoimmune arthritis in mouse models, the underlying activity of BAMBI on the human Th17/Treg cell axis, particularly during exposure to cigarette smoke, remains to be elucidated. The present study aimed to further characterize BAMBI expression in human CD4+ cells, as well as immune imbalance during activation and cigarette smoke exposure. Results from the present study indicated that exposure to cigarette smoke extract partially suppressed Treg differentiation and promoted Th17 cell generation under stimulation by anti-CD3/28 antibodies and TGF-β1. Additionally, exposure to cigarette smoke induced an inhibition of phosphorylated-Smad2/Smad3, which may have arisen from a concomitant enhancement of BAMBI expression. In conclusion, human BAMBI may function as a molecular switch to control TGF-β signalling strength and the Th17/Treg cell balance, which may be used not only as a biomarker but also as a target of new treatment strategies for maintaining immune tolerance and for the treatment of smoking-induced immune disorders.

The lungs are one of the most common organs to which cancer metastasizes, but are a location not common for uterine sarcoma. A malignant mixed Müllerian tumor (MMMT) of the uterus is an extremely rare and aggressive sarcoma, characterized by a mixture of epithelial and mesenchymal components. There are few reports regarding the pulmonary metastasis from MMMTs. The present study presents the case of a 58-year-old woman with hemoptysis and post-menopausal vaginal bleeding. The woman was initially diagnosed with invasive aspergillosis based on a chest computed tomography (CT) scan showing multiple pulmonary nodular opacities surrounded by a ground-glass attenuation halo (halo-sign). Diagnostic curettage and a percutaneous CT-guided lung biopsy were conducted for the pathological diagnosis. Finally, the diagnosis was confirmed as MMMT with lung metastasis based on the histopathological examination of cervical canals, uterus and lung specimens, which showed a mixture of carcinomatous and sarcomatous elements, and morphology exhibiting hyperchromatic nuclei and necrosis. Immunohistochemical staining was positive for vimentin, focally positive for p16, and negative for napsin, cytokeratin 7 (CK7), CK20, carcinoembryonic antigen, carbohydrate antigen 125, homeobox protein CDX2 and villin in the lung specimens. This case highlights that pulmonary metastatic tumor from uterine sarcoma can present as halo-sign, which is commonly observed in pulmonary aspergillosis. Therefore, it needs to be considered in the differential diagnosis of such lesions, and pathological confirmation is required.

Adult lymphoblastic lymphoma (LBL) is an aggressive form of non-Hodgkin lymphoma occurring in predominantly adolescent and young adult men, accounting for 1% to 2% of all non-Hodgkin's lymphomas. In contrast to B-LBL, T-cell LBL is much more common, accounting for up to 90% of disease in adults. Mediastinal mass, pleural and/or pericardial effusions are the major characteristics of T-LBL. We report an 18-year-old male with a pleural effusion, mediastinal mass, a light pericardial effusion, and a normal hemogram. The cytology of the pleural effusion initially suggested malignancy, but definitive diagnosis was unclear. After a medical thoracoscopy, the partial pleura was picked and immunophenotypic study revealed the following: CD3+, TdT+, CD99+, CD20−. The patient was finally diagnosed with T-LBL and died only 6 months after that. The case highlight the point that medical thoracoscopy is a safe and accurate diagnostic procedure for pleural diseases, and partial pleura biopsy with immunophenotyping was essential for achieving the correct diagnosis of LBL.

Radiation leads to a rapid burst of reactive oxygen species (ROS), which is considered to be one of the major causes of radiation-induced injury. ROS have previously been shown to induce changes in cytosolic Ca2+ ([Ca2+]i) including [Ca2+]i oscillation. However, the role of radiation in [Ca2+]i oscillation is poorly understood. The purpose of this study was to identify the effect of ROS and X ray on [Ca2+]i oscillation, as well as their role in radiation-induced lung injury. Alveolar macrophages were cultured in the absence and presence of different doses of hydrogen peroxide (H2O2) or exposed to X-ray irradiation with or without pretreatment of diphenyleneiodonium chloride (DPI, an inhibitor of NADPH oxidases) or tetrandrine (TET, a calcium entry blocker) and cytosolic Ca2+ concentration was detected by fluorescent Ca2+ indicator Fura-2. Rat radiation lung injury was induced in vivo by using 40 Gy X ray and DPI or TET was used to prevent radiation-induced lung injury. The results showed that there was sp...

Radiation leads to a rapid burst of reactive oxygen species (ROS), which is considered to be one of the major causes of radiation-induced injury. ROS have previously been shown to induce changes in cytosolic Ca²⁺ ([Ca²⁺]i) including [Ca²⁺]i oscillation. However, the role of radiation in [Ca²⁺]i oscillation is poorly understood. The purpose of this study was to identify the effect of ROS and X ray on [Ca²⁺]i oscillation, as well as their role in radiation-induced lung injury. Alveolar macrophages were cultured in the absence and presence of different doses of hydrogen peroxide (H₂O₂) or exposed to X-ray irradiation with or without pretreatment of diphenyleneiodonium chloride (DPI, an inhibitor of NADPH oxidases) or tetrandrine (TET, a calcium entry blocker) and cytosolic Ca²⁺ concentration was detected by fluorescent Ca²⁺ indicator Fura-2. Rat radiation lung injury was induced in vivo by using 40 Gy X ray and DPI or TET was used to prevent radiation-induced lung injury. The results showed that there was spontaneous [Ca²⁺]i oscillation in alveolar macrophages under normal conditions, and treatment of H₂O₂ (100-500 μM) or 2 Gy X ray inhibited the spontaneous [Ca²⁺]i oscillation and induced [Ca²⁺]i rise. TET abolished H₂O₂ or X ray induced [Ca²⁺]i rise in alveolar macrophages, and attenuated X ray- induced rat alveolitis in vivo. DPI prevented X-ray-induced inhibition of [Ca²⁺]i oscillation in alveolar macrophages and prevented X-ray-induced rat alveolitis. Taken together, the data suggest that the disruption of [Ca²⁺]i oscillation and induction of [Ca²⁺]i rise through ROS is involved in the mechanism of radiation-induced lung injury.

The diagnosis of tuberculous pleurisy by analysis of pleural fluid using standard diagnostic tools is difficult. Recently, T-cell interferon-γ release assays (IGRA) have been introduced for the diagnosis of tuberculous pleurisy. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of IGRA on both pleural fluid and peripheral blood, for diagnosing tuberculous pleurisy.A systematic review was performed of English language publications. Sensitivity, specificity and other measures of the accuracy of IGRA for the diagnosis tuberculous pleurisy using both pleural fluid and blood were pooled using a random-effects model or a fixed-effects model. Receiver operating characteristic curves were used to summarize overall test performance.Seven out of eight studies met the inclusion criteria. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value and diagnostic odds ratio were, for pleural fluid: 0.75, 0.82, 3.49, 0.24, 0.85, 0.70 and 19.04, respectively; and for blood: 0.80, 0.72, 2.86, 0.28, 0.78, 0.74 and 11.06, respectively.As almost 20% of non-tuberculosis patients would be erroneously treated for tuberculosis and 25% of patients with tuberculous pleurisy would be missed, pleural fluid IGRA are not useful for the clinical diagnosis of tuberculous pleurisy.

To explore the anti-tumor immune responses of dendritic cells (DCs) loaded with intact wild-type p53 to mice challenged with tumor cells expressing p53 genes with mutations at different sites.Ad-p53-DC immunization function was assessed by the expression of surface molecules and allogeneic MLR. DCs derived from bone marrow were transduced with adenovirus or a human wild-type p53 containing recombinant adenovirus (Ad-DC and Ad-p53-DC) and immunized C57BL/6 mice. Splenocytes were separated and cell cytotoxicity was measured against tumor cells expressing mutant p53 (MethA, D459 and P815) in a standard 6-h(51)Cr-release assay. Effector and target cells were incubated in the presence of anti-CD(4) or anti-CD(8) antibody. Ad-p53-DC was immunized in control Ad-DC before or after mice were challenged with either D459 tumor or with MethA sarcoma cells to observe whether immune response would provide tumor protection.Immunization with Ad-p53-DC developed significantly higher substantial CTL responses against Ad-p53-P815, D459 and MethA cells (effectors: target cells = 50:1), (27.8 +/- 3.4)%, (23.5 +/- 2.7)%, (58.3 +/- 9.2)% than with Ad-DC (9.3 +/- 1.8)%, (4.6 +/- 1.0)%, (23.5 +/- 3.7)% (t(d) = 5.79, 3.68, 5.02, all P0.05). In Ad-p53-DC immunized mice, anti-CD(8) antibody blocked the cytotoxicity against Ad-p53-P815 (26.7 +/- 2.8)% or D459 (6.1 +/- 1.2)%, but not anti-CD(4) antibody [(59.8 +/- 4.6)%, (18.9 +/- 2.4)%, t(d) = 8.79 or 9.18, all P0.05]. Ad-p53-DC immunization provided complete tumor protection in 80% of mice challenged with D459 and in 70% of mice challenged with MethA, while none protected in Ad-DC immunization group (chi(2) = 6.72, 5.86, all P0.05). Treated with Ad-p53-DC after D459 inoculation subcutaneously, mice were killed due to the bulky tumor more than 2 weeks later than the mice in the Ad-DC treatment group during 7 week observation (chi(2) = 9.48, P0.05).DCs transfected with 100 MOI Ad-p53 induced intense CTL responses against P815, D459 and MethA. This CTL response is mediated by CD(8)(+) T cells. Treatment with Ad-p53-DC significantly developed tumor immunology and slowed the growth of established tumors.

To investigate the effect of AP-1 Decoy on matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-1) imbalance induced by bleomycin-A5 (BLM-A5) in pulmonary fibroblasts.Pulmonary fibroblasts were primary cultured, and transferred with AP-1 Decoy before treated with BLM-A5. MMPs activity in medium was determined by gelatin zymography. Protein content of TIMP-1 in medium was detected by ELISA. Expression of MMP-2 mRNA and TIMP-1 mRNA were determined by reverse transcriptase-polymerase chain reaction (RT-PCR).BLM-A5 induced the increase in activity of MMP-2 at 12 h [A: (0.77 +/- 0.08) vs (0.65 +/- 0.07) P0.05], but it was suppressed by AP-1 Decoy [A: (0.68 +/- 0.05)]. BLM-A5 up-regulated the expression of protein and mRNA of TIMP-1 after 12 h, and 24 h [(39.3 +/- 4.3), (46.3 +/- 4.8) ng/ml vs (28.9 +/- 2.7), (31.6 +/- 2.4) ng/ml] and [Absorbance ratio to beta-actin: (0.94 +/- 0.13, 1.08 +/- 0.06) vs (0.76 +/- 0.07, 0.75 +/- 0.08)] (P0.05 or P0.01) but AP-1 Decoy modulated the up-regulation. All these indexes in AP-1 Decoy group had no significant difference in contrast to the normal group. Mutant AP-1 Decoy had not the same function as AP-1 Decoy on the expression of MMP-2 and TIMP-1 in pulmonary fibroblasts.AP-1 Decoy inhibits the increase in MMP-2 activity and the up-regulation of TIMP-1 induced by BLM-A5 in pulmonary fibroblasts.

To investigate the role of found in inflammatory zone 1 (FIZZ1) protein in the pathogenesis of experimental pulmonary fibrosis, 48 male Sprague-Dawley rats were randomly divided into two groups, the pulmonary fibrosis group and the control group. Rat pulmonary fibrosis was reproduced by an intratracheal injection of bleomycin (5 mg/kg body weight). Normal saline (1 ml/kg body weight) was given intratracheally injection in the control group. There were 24 rats in each group, and 6 animals were separately killed on the 7th, 14th, 21th and 28th day after treated with bleomycin or normal saline. Then the following tests were undertaken: (1) HE and Masson staining of lung section;(2) Determination of lung tissue hydroxyproline (HYP);(3) Immunohistochemical staining of protein of FIZZ1 in the lung;(4) In situ hybridization of FIZZ1 mRNA in the lung. The results showed: (1) There were full of inflammatory cells in the lung, the interval of alveoli enlarged and many alveolar spaces disappeared on the 7th day after treated with bleomycin in the fibrosis group. Collagen began to proliferate after 14 d. The pulmonary fibrosis was stably established on the 28th day, full of green fibers in the Masson staining of lung section. (2) The expression of FIZZ1 protein in the lung increased after 7 d in bleomycin-treated animals (3.013+/-0.326 vs 0.473+/-0.056, P0.01 vs control), but was slightly decreased on the 14th day (2.124+/-0.197) and expensively decreased on the 21st day (1.760+/-0.105) and the 28th day (0.691+/-0.081). (3) The expression of FIZZ1 mRNA in the lung also increased after 7 d by treated with bleomycin (3.795+/-0.338 vs 0.678+/-0.087, P0.01 vs control), but decreased on the 14th day (1.276+/-0.104) and further decreased on the 28th day (0.896+/-0.084). The expression of FIZZ1 protein and mRNA in fibrosis group was higher than that in the control group (P0.05 or P0.01). The results suggest that FIZZ1 protein and FIZZ1 mRNA are dynamically changed in the lung with experimental pulmonary fibrosis, which may contribute to the pathogenesis of pulmonary fibrosis.

To explore the effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the growth of human lung cancer cell lines and its possible mechanism.Human non-small cell lung cancer (NSCLC) cells of the A549 line and human small cell lung cancer (SCLC) of the LTEP-P line were cultured and were divided into 3 groups respectively: control group, 15d-PGJ(2) group (15d-PGJ(2), a PPAR-gamma activator, was added), and ciglitazone group (ciglitazone, am antidiabetic drug, was added). Twenty-four, forty-eight, and seventy-two hours later, nested RT-PCR was used to detect t the expression of PPAR-gamma mRNA, Western blotting technique was used to detect the expression of PPAR-gamma protein, MTT staining was used to observe the proliferation of cells induced by PPAR-gamma agonists, TUNEL method was used to observe the apoptosis of cells affected by the ligands of PPAR-gamma, the expressions of bax, and bcl-2 mRN and proteins were examined by in situ hybridization and immunohistochemistry, and the expression of caspase-3 was detected by immunohistochemistry.PPAR-gamma was expressed in the two lung cancer cell lines. The cell proliferation was inhibited by 15d-PGJ(2) and ciglitazone, especially the former, in dose-dependent and time-dependent manners. The apoptosis rates were (1.9 +/- 0.5)%, (9.8 +/- 1.5)%, and (5.6 +/- 1.1)% respectively in the control, 15d-PGJ(2), and ciglitazone groups with a significant difference between ant 2 groups (all P0.05). The expression rate of bax were (9,2 +/- 1.5)%, (63 +/- 10)%, and (31 +/- 6)% respectively in the control, 15d-PGJ(2), and ciglitazone groups with a very significant difference between ant 2 groups (all P0.01). he expression rate of bcl-2 were (18 +/- 3)%, (36 +/- 9)%, and (33 +/- 7)% respectively in the control, 15d-PGJ(2), and ciglitazone groups with a very significant difference between the control group and any of the agonist-treated groups (all P0.01) and without significant difference between the two treated groups. The expression rates of caspase-3 were (6.5 +/- 1.0)%, (65 +/- 11)%, and (40 +/- 7)% respectively in the control, 15d-PGJ(2), and ciglitazone groups with a significant difference between any 2 group (all P0.01). The caspase-3 level was positively correlated with the level of apoptosis.Activated by ligands, PPAR-gamma remarkably inhibits the growth of human lung cancer cells through inducing apoptosis. Caspase-3 and bax/bcl-2 play a role in this process, PPAR-gamma is so important in the pathogenesis and/or progression of lung cancer that it may be a novel therapeutical target against lung cancer.