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Pulmonary fibrosis (PF) is a chronic respiratory inflammation disease that threatens human health. The topical immune microenvironment of lung tissue regulates progression of fibrosis. In this study, the efficacy and molecular mechanism of suplatast tosilate (ST) against PF were observed. ST is a T helper 2 (Th2) cytokine inhibitor for clinical treatment of bronchial asthma. But whether it can be applied to therapy of chronic PF and the biomechanism of ST inhibiting Th2 cytokine release are not clear. Using in vivo and in vitro experiments, we found that ST can significantly suppress the pathogenesis of chronic PF induced by multiple bleomycin injury, improve the lung function, and decrease the deposition of collagen in lung tissue. In addition, ST decreases Th2 cytokine releasing through restraining Th2 cell differentiation in the meantime, but did not influence the T helper 1 (Th1) cell differentiation and Th1 cytokine releasing. Further studies showed that ST inhibits Th2 cell differentiation by down-regulating GATA-binding protein 3 (GATA3) expression and activity through inhibiting the phosphorylation of signal transducer and activator of transcription 5 (STAT5) and mammalian target of rapamycin (mTOR). The excessive expression of GATA3 in lungs can reverse the anti-PF effect of ST. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Our research not only clarifies the pharmacological mechanism of ST, but also provides a new selection for clinical anti-PF drug therapy.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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