Tumor Necrosis Factor‐ <i>α</i> Induces Human Bronchial Fibroblasts to Produce Cytokines: Implications for Airway Inflammation

ABSTRACT 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.