Tumor necrosis factor-α induces human bronchial fibroblasts to produce cytokines: implications for airway inflammation

Pulmonary fibroblasts coordinate the progression of airway inflammation through multiple pathways. However, the role and underlying mechanisms of its subtype, bronchial fibroblasts, under TNF-α induction remain unclear. This study found that TNF-α was highly expressed in the airway with asthma patients. Gene sequencing found that a large number of inflammatory cytokines were expressed in TNF-α induced human bronchial fibroblasts, such as IL-6, IL-1β, IL-15, TNF, CX3CL1, DAPK2, TSLP, CCL2, CCL5, CCL7, CXCL1, CXCL2, CXCL3, CXCL5, and CXCL6, which are closely related to eosinophil or neutrophil inflammation. GO enrichment pathways based on the background of the upregulated DEGs showed that TNF-α-induced bronchial fibroblasts are closely associated with the programmed cell necrosis signaling, Th2 cytokines production, eosinophils, neutrophils and so on. Then, western blot showed that the expression levels of IL-1β and TNF-α in TNF-α-induced bronchial fibroblasts considerably increased, and the expression levels of fibronectin, COL1A1, and TGFβ1 were substantially decreased. ELISA results showed that CCL2, CCL5, CCL7, TSLP, CXCL1, CXCL2, IL-6, and IL-1β levels were considerably increased under TNF-α-induced bronchial fibroblasts supernatant. In conclusion, our study results indicate that TNF-α-induced bronchial fibroblasts play an important role in airway inflammation.