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.
Assuntos
Bacteroides , Transição Epitelial-Mesenquimal , Escherichia coli , Lipopolissacarídeos , Pulmão , Lipopolissacarídeos/química , Escherichia coli/química , Escherichia coli/fisiologia , Bacteroides/química , Bacteroides/fisiologia , Acilação , Inflamação , Células A549 , Pulmão/patologia , Transdução de Sinais , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Background: Atherosclerosis (AS) is a pathological vascular disorder responsible for the majority of cardiovascular deaths. Sarsasapogenin (Sar) is a natural steroidal compound which has been extensively applied to multiple human diseases due to its pharmacological properties. In the present paper, the impacts of Sar on oxidized low-density lipoprotein (ox-LDL)-treated vascular smooth muscle cells (VSMCs) and its possible action mechanism were investigated. Methods: Firstly, Cell Counting Kit-8 (CCK-8) estimated the viability of VSMCs following treatment with ascending doses of Sar. Then, VSMCs were treated by ox-LDL to stimulate an in vitro cell model of AS. CCK-8 and 5-Ethynyl-2'-deoxyuridine (EDU) assays were used to assess cell proliferation. Wound healing and transwell assays were applied to measure the migratory and invasive capacities, respectively. The expression of proliferation-, metastasis-, and stromal interaction molecule 1 (STIM1)/Orai signaling-associated proteins was measured by western blot. Results: The experimental data illuminated that Sar treatment noticeably protected against ox-LDL-elicited VSMCs proliferation, migration, and invasion. Besides, Sar lowered the elevated STIM1 and Orai expression in ox-LDL-treated VSMCs. Further, STIM1 elevation partially abrogated the impacts of Sar on the proliferation, migration, and invasion of VSMCs challenged with ox-LDL. Conclusions: In conclusion, Sar might reduce STIM1 expression to impede the aggressive phenotypes of ox-LDL-treated VSMCs.
RESUMO
BACKGROUND: The most common mechanisms of multidrug resistance (MDR) in cancer cells is the expression of an energy-dependent exfflux pump. P-glycoprotein (P-gp) encoded by MDR1 gene and multidrug associated protein (MRP) are well known proteins associated with MDR. In human cancers, the MDR1 gene expression is common in patients with intrinsic and acquired MDR. It is a major therapeutic problem in cancer chemotherapy. Previously we found that the MDR of HCC is related to MRP gene expression and initiates the intrinsic MDR. The aim of this study is to study the expression of MDR1 gene encoding P-gp and MDRl mRNA in primary gallbladder carcinoma, and analyze its clinical significance. METHODS: Immunohistochemistry (IHC) S-P method and in situ polymerase chain reaction (ISPCR) were used to detect the expression of P-gp and MDR1 mRNA in 53 cases of untreated primary gallbladder carcinoma and 12 cases of cholecystitis (archival paraffin-embedded tissues). RESULTS: The positive expression rates of P-gp and MDR1 mRNA in the 53 cases and 12 cases were 60.38%, 71.69% and 25.00%, 33.33%, respectively. There was a significant difference between the two groups (P<0.05). The positive expression rate of P-gp and MDR1mRNA were 69.44%, 83.33% and 41.18%, 47.06% respectively in tissues in stage of Nevin I-III against Nevin IV, V (P<0.05). In well, moderately differentiated gallbladder carcinoma tissues, their expressions were 79.49%, 69.23% against 50.00%, 35.71% in low, undifferentiated tissues (P<0.05). CONCLUSIONS: MDR to gallbladder carcinoma is closely related to the intrinsic MDR and it provides an important evidence to reverse the MDR by detection of the MDR1 gene. Meanwhile, MDR1 gene expression in gallbladder carcinoma is correlated with some biological characteristics, takes part in the carcinogenesis of gallbladder tissues, and acts as a valuable biomarker of prognosis.