IL-37 Alleviates Mechanical Stretch-induced Lung Epithelial Cells Injury And Epithelial-mesenchymal Transition

[Background]As an important treatment,mechanical ventilation is widely used in Acute lung injury,Acute respiratory distress syndrome and other diseases with high incidence and mortality in intensive care unit.However,inappropriate mechanical ventilation can lead to ventilator-associated lung injury and eventually lung fibrosis.Myofibroblasts,as the key cells to regulate the process of lung fibrosis,are mainly activated by local epithelial-mesenchymal transition.Interleukin-37 is a cytokine that inhibits inflammation and fibrosis,but there is no related research on the effect of mechanical stretch.In this study,we take human lung epithelial cells as the main research object,through in vitro experiments to induce human lung epithelial cell epithelial-mesenchymal transition,to explore the role of IL-37 in mechanical stretch lung epithelial cells.[Objectives]To study the expression of IL-37 in human lung epithelial cells induced by mechanical stretch and the inhibitory effect of IL-37 on EMT,to find a possible and effective target for the clinical treatment of ventilator induce lung injury.Patients can benefit more from mechanical ventilation by reducing lung injury and even lung fibrosis.[Methods]BEAS-2B cells were cultured in vitro,then stretch the BEAS-2B cells with FX-5000 system for a period of 24,48 and 72h(sinusoidal pattern,20% elongation,0.33Hz).The protein expressions of E-cadherin,α-SMA,Vimentin,N-cadherin and IL-37 were detected by Western blot and Immunofluorescence respectively.At the same time,the m RNA and protein levels of IL-6,TNF-α and TGF-β1were detected by quantitative polymerase chain reaction(q PCR)and Enzyme-Linked Immunosorbent Assay(ELISA).BEAS-2B cells were pretreated with recombinant protein IL-37 and then subjected to 20% elongation for 48 h.Then the expression of EMT-related markers protein and inflammatory cytokine were detected as mentioned above.[Results]The 20% elongation could induced EMT in BEAS-2B cells after stretch for 48 h,and the expression of E-cadherin,and IL-37 decreased,the expression of α-SMA,Vimentin,N-cadherin,TGF-β1,IL-6 and TNF-α increased in a time-dependent manner(P<0.05).Pre-treated with IL-37 could partially reverse the occurrence of EMT,increase the expression of epithelial marker protein E-cadherin and decrease the expression of interstitial marker protein α-SMA,Vimentin and N-cadherin,and inhibit the expression of inflammatory cytokine IL-6,TNF-α and TGF-β 1.[Conclusions]Mechanical stretch with 20% elongation can induce EMT and increase the expression of inflammatory cytokine in human lung epithelial cells BEAS-2B by inhibiting the expression of IL-37.Pretreated with recombinant protein IL-37 tends to reduce EMT and inhibit the expression of inflammatory cytokine.IL-37 deficiency may be a new important pathogenesis and potential therapeutic target of ventilator-induced lung injury.