P38a contributes to TNF-a-induced IL-8 production in human gingival cells

Tumor necrosis factor-alpha (TNF-a) is a major inflammatory cytokine that induces interleukin (IL)-8 production. Although some studies have reported the involvement of the p38 MAPK signaling pathway in TNF-a-induced IL-8 production, its specific regulatory mechanisms in gingival epithelial cells (GECs) are still poorly understood. In the present study, Ca9-22 cells were used as representative GECs to investigate the effect of p38 signaling on TNF-a-induced IL-8 production. We found that TNF-a enhanced IL-8 production in Ca9-22 cells by activating the p38 signaling pathway, and one of its isoforms, p38a, played a key role. P38a deletion markedly inhibited TNF-a-induced IL-8 expression in Ca9-22 cells, while p38a gene rescue could reverse this effect. Further studies revealed that TNF-a-induced IL-8 production was markedly reduced when the threonine 180 and tyrosine 182 p38a phosphorylation sites were targeted for mutagenesis to alanine and phenylalanine, respectively, suggesting their critical role in the process. In conclusion, p38a plays an important role in TNF-a-induced IL-8 production, providing a potential therapeutic target to prevent and treat periodontal disease.

Automated summary

The p38a isoform is crucial for TNF-a-induced IL-8 production in Ca9-22 cells, and its activation is associated with the phosphorylation of threonine 180 and tyrosine 182. This study highlights p38a as a potential therapeutic target for preventing and treating periodontal disease.