EGFR-INDUCED ERK1/2 AND P38 ACTIVATION OF THE MAPK SIGNALING PATHWAY CAUSES TNF-A PRODUCTION AND RELEASE AND PROMOTES ACUTE LUNG INJURY

Objective: To analyze the activation of ERK1/2 and P38 induced by epidermal growth factor receptor (EGFR) in the MAPK signaling pathway to induce the generation and release of tumor necrosis factor alpha (TNF-alpha) and promote the occurrence of acute lung injury. Methods: 42 male SPF grade mice were selected, and 10 mice were divided into a normal group and a model group. The model group used lipopolysaccharide (2 mg/kg) to establish the ALI model. A western blot detected EGFR protein expression in the lung tissues of the two groups. The remaining 32 mice were randomly divided into a normal group, a positive control group (EGFR inhibitor erlotinib 100 mg/ kg gavage), a model group (lipopolysaccharide 2 mg/kg modeling), and an EGFR inhibitor group (lipopolysaccharide + EGFR inhibitor erlotinib). The HE staining method was used to detect changes in lung tissue structure of ALI mice in each group, and the ELISA method was used to detect serum TNF-alpha levels in each group, and a western blot was used to detect ERK1/2 and P38 phosphorylation levels in each group. Results: EGFR was expressed in the normal mice and the ALI model mice. The expression of p-EGFR protein in the model group was significantly higher than in the control group, and the p-EGFR/EGFR ratio was significantly higher than the that of the control group. The difference was statistically significant (P<0.05). In the model group, the lung tissue was seriously damaged, and the alveolar structure was destroyed, accompanied by a large amount of inflammatory cell infiltration and erythrocyte exudation. The lung tissue damage in the EGFR inhibitor group was significantly lower, and the normal alveolar structure was visible. The serum TNF-alpha expressions in the model group and the EGFR inhibitor group were significantly higher than those of the normal group and the positive control group (P<0.05). The expression of serum TNF-alpha in the EGFR inhibitor group was significantly lower than that in the model group, and the difference was statistically significant (P<0.05). The phosphorylation levels of ERK1/2 and P38 in the model group and the EGFR inhibitor group were significantly higher than those in the normal group (P<0.05). In addition, the phosphorylation levels of ERK1/2 and P38 in the EGFR inhibitor group were significantly lower than that in the model group, and the difference was statistically significant (P<0.05). Conclusion: EGFR participates in the production and release of TNF-alpha induced by ALI. This mechanism may occur through the activation of ERK1/2 and P38 levels in the MAPK signaling pathway. Thus, the phosphorylation of ERK1/2 and P38 may promote the occurrence of ALI.