MUC1 (mucin 1), a membrane‐tethered mucin glycoprotein, is highly expressed on the surface of respiratory epithelial cells and plays a key role in anti‐inflammatory and antiapoptotic responses against infections. However, little is known about the link between MUC1 and necroptosis in asthma. This study aimed to investigate the effects of MUC1 on TNF‐α‐induced necroptosis in human bronchial epithelial (16HBE) cells and the underlying molecular mechanism. Negative control and MUC1‐siRNA cells were treated with TNF‐α in the presence or absence of necrostatin‐1 (Nec‐1). Necroptosis was investigated using flow cytometry analyses, and the protein expression levels of MUC1, receptor‐interacting protein kinase‐1 (RIPK1), RIPK3, and phosphorylated RIPK1 were detected by western blot analysis. In addition, the interactions between RIPK and MUC1 were analyzed by coimmunoprecipitation. The results demonstrated that TNF‐α could induce necroptosis of 16HBE cells, and MUC1 expression was increased upon treatment with TNF‐α. The coimmunoprecipitation outcomes showed that MUC1 interacted with RIPK1 but not with RIPK3 in 16HBE cells, and the interaction was augmented by TNF‐α. Furthermore, MUC1 downregulation obviously increased the TNF‐α‐induced necroptosis of 16HBE cells and enhanced the expression of p‐RIPK1‐Ser166 and RIPK3, whereas these phenomena were partially attenuated by Nec‐1. These results may provide a new insight into the mechanism of severe asthma‐related necroptosis and lay a foundation for the future development of new anti‐inflammatory drugs for asthma.

Abstractα5β1 integrin is highly expressed in airway smooth muscle cells and mediate the adhesion of airway smooth muscle cells to fibronectin to regulate airway remodelling in asthma. This study aimed to investigate the effects of synthetic cyclic peptide *CRRETAWAC* on fibronectin‐induced cytokine secretion of airway smooth muscle cells and the underlying mechanism. Human airway smooth muscle cells were isolated and treated with fibronectin, IL‐13, *CRRETAWAC* peptide, α5β1 integrin‐blocking antibody, FAK inhibitor or p38 MAPK inhibitor. The transcription and secretion of eotaxin‐1 and RANTES were detected by real‐time PCR and ELISA, respectively. The phosphorylation of FAK and MAPKs including p38, ERK1/2 and JNK1/2 was detected by Western blot analysis. The transcription and secretion of eotaxin‐1 and RANTES increased in airway smooth muscle cells cultured in fibronectin‐coated plates. However, α5β1 integrin‐blocking antibody, *CRRETAWAC* peptide, FAK inhibitor or p38 MAPK inhibitor significantly reduced mRNA levels and the secretion of eotaxin‐1 and RANTES in airway smooth muscle cells cultured in fibronectin‐coated plates. In addition, the phosphorylation of FAK and p38 MAPK was significantly increased in airway smooth muscle cells cultured in fibronectin‐coated plates compared to the cells cultured in uncoated plates and was significantly reduced in airway smooth muscle cells treated with *CRRETAWAC* peptide. Fibronectin induces cytokine synthesis and secretion of airway smooth muscle cells. Peptide *CRRETAWAC* antagonizes fibronectin‐induced cytokine synthesis and secretion of airway smooth muscle cells via the inhibition of FAK and p38 MAPK, and is a potential agent for the therapy of asthma.