Doxycycline attenuates paraquat-induced pulmonary fibrosis by downregulating the TGF-β signaling pathway

Background: Paraquat (PQ) is a highly efficient herbicide that remains widely used in agriculture. However, the inappropriate application of this herbicide may cause multiple organ injuries including pulmonary injury. In this study, we report that doxycycline (Doxy) treats PQ-induced pulmonary fibrosis (PF). Methods: Mice with PQ-induced PF were treated with different doses of Doxy by intragastric administration. Human lung cancer cell line A549 pre-treated with TGF-beta 1 (5 ng/mL) were treated with Doxy hydrochloride (3.4 mu M). Results: PF was observed from day 28 in PQ-treated group and Doxy treatments significantly reduced pulmonary coefficient, histopathological score and collagen content in a dose-dependent manner. Doxy can inhibit the expression levels of plasma inflammation cytokines at day 28 after modeling and reduced inflammatory response at early stage of PQ-induced lung injury. Immunohistochemical staining assay and proteomic analysis indicated that Doxy could restore ectopic epithelial-mesenchymal transition (EMT) induced by PQ-treatment by regulating numerous TGF-beta signaling related proteins. Conclusions: The findings suggest that Doxy can restore the balance of epithelial-mesenchymal cells and attenuate PQ-induced PF by downregulating the TGF-beta signaling pathway.