Role of the TLR4-MyD88-NF-κB signaling pathway in the development of cow's milk protein allergy
Objective To investigate the role of the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa-B (NF-κB) signaling pathway in the pathogenesis of cow's milk protein allergy (CMPA). Methods Thirty children diagnosed with CMPA who were treated at Hangzhou Children's Hospital from November 2020 to June 2023 were selected as the experimental group. An additional 30 healthy children,undergoing routine check-ups or elective surgeries during the same period,were included as controls. Venous blood was collected from children with CMPA before and after dietary avoidance treatment and from normal control children. Western blot was used to detect the protein expression levels of TLR4,MyD88,and NF-κB p65. Flow cytometry and ELISA were used to detect the levels of cellular inflammatory factors and milk-specific IgE. Spearman's rank correlation analysis was applied to determine the correlations between TLR4,MyD88,and NF-κB p65 protein expression levels,and between their expression and inflammatory cytokine levels in CMPA patients prior to dietary intervention. Results CMPA patients exhibited significantly higher expressions of TLR4,MyD88,NF-κB p65 proteins,along with elevated levels of IL-1β,IL-5,and IL-6,compared to their post-treatment levels and the control group (all P<0.05). Spearman's analysis indicated positive correlations between TLR4 and NF-κB p65 levels and MyD88 protein expression (rs=0.496,0.488,P=0.005,0.006),as well as between IL-1β and IL-6 levels and NF-κB p65 protein expression (rs=0.475,0.394,P=0.008,0.031);while no significant correlation was observed between NF-κB p65 and IL-5 levels (rs=0.167,P=0.378). There were no significant differences in the positive rates of milk-specific IgE between CMPA patients and the controls,either before or after dietary intervention (all P>0.05). Conclusion The TLR4-MyD88-NF-κB signaling pathway plays a crucial role in the pathogenesis of CMPA,which is positively correlated with pro-inflammatory cytokines IL-1βand IL-6. Targeting this pathway may represent a promising therapeutic strategy for mitigating CMPA symptoms.
万方数据
维普
