The interleukin-23 (IL-23) plays a key role in various inflammatory diseases, such as spondyloarthritis, by acting on target cells through the IL-23/IL-17 pathway. Recent studies have suggested that IL-23 can also directly affect fibroblasts. Senescent fibroblasts are implicated in many physiological and pathological processes, including those related to inflammatory diseases. However, it remains unclear whether IL-23 can influence fibroblast senescence and contribute to pathogenesis. In our study, we investigated the effects of IL-23 on oxidative stress-induced senescence in human fibroblasts, using the H2O2-induced senescence model, and found that IL-23 pre-treatment significantly attenuated senescence in these cells. RNA-seq and in vitro experiments indicate that IL-23 may act by regulating GADD45a expression and the p38/MAPK pathway. Furthermore, we confirmed that IL-23 inhibits oxidative stress-induced up-regulation of GADD45a expression and subsequent activation of the p38/MAPK pathway through GADD45a knockdown and overexpression experiments. Our study is the first to demonstrate that IL-23 can effectively suppress the senescence of fibroblasts induced by oxidative stress, by inhibiting the H2O2-triggered induction of GADD45a and subsequent activation of the p38/MAPK pathway. These findings have significant implications for understanding the role of IL-23 in immune-inflammatory diseases and may provide a new avenue for the diagnosis and treatment of these conditions.
Keywords: Cellular senescence; Fibroblasts; GADD45a; Interleukin-23.
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