RESUMO
Pathological epithelialmesenchymal transition (EMT) has been shown to fulfill a key role in the development and progression of a variety of lung diseases. It has been demonstrated that the inflammatory microenvironment is a decisive factor in inducing pathological EMT. Hexacylated lipopolysaccharide (LPS) [or proacylated lipopolysaccharide (PLPS), which functions as proinflammatory lipopolysaccharide] is one of the most effective Tolllike receptor 4 (TLR4) agonists. Furthermore, the pentacylated and tetracylated form of lipopolysaccharide (or ALPS, which functions as antiinflammatory lipopolysaccharide) has been shown to elicit competitive antagonistic effects against the proinflammatory activity of PLPS. At present, it remains unclear whether LPS extracted from Bacteroides vulgatus (BVLPS) can prevent LPS extracted from Escherichia coli (ECLPS) from inducing pathological EMT. In the present study, A549 cells and C57BL/6 mice lung tissue were both induced by ECLPS (PLPS) and BVLPS (ALPS), either alone or in combination. The anticipated antiinflammatory effects of BVLPS were analyzed by examining the lung coefficient, lung pathology, A549 cell morphology and expression levels both of the inflammatory cytokines, IL1ß, IL6 and TNFα and of the EMT signature proteins, epithelial cadherin (Ecadherin), αsmooth muscle actin (αSMA) and vimentin. In addition, the expression levels of TLR4, bone morphogenic protein and activin membranebound inhibitor (BAMBI) and Snail were detected and the possible mechanism underlying how BVLPS may prevent ECLPSinduced EMT was analyzed. The results obtained showed that the morphology of the A549 cells was significantly polarized, the lung index was significantly increased, the alveolar structure was collapsed and the expression levels of IL1ß, IL6, TNFα, αSMA, vimentin, TLR4 and Snail in both lung tissue and A549 cells were significantly increased, whereas those of Ecadherin and BAMBI were significantly decreased. Treatment with BVLPS in combination with ECLPS was found to reverse these changes. In conclusion, the present study demonstrated that BVLPS is able to effectively prevent ECLPSinduced EMT in A549 cells and in mouse lung tissue and furthermore, the underlying mechanism may be associated with inhibition of the TLR4/BAMBI/Snail signaling pathway.