Collagen I-induced dendritic cells activation is regulated by TNF-α production through down-regulation of IRF4
2015
Poudel, Barun | Ki, Hyeon-Hui | Lee, Young-Mi | Kim, Dae-Ki
Previously we have shown that collagen I enhances the maturation and function of dendritic cells (DCs). Inflammatory mediators such as tumour necrosis factor (TNF)-α, interleukin (IL)-1β and lipopolysaccharide (LPS) are also known to activate DCs. Here we investigated the involvement of TNF-α on the collagen I-induced DCs activation. TNF-a neutralization inhibited collagen I-induced IL-12 secretions by DCs. Additionally, we observed suppression of collagen I-induced costimulatory molecules expression along with down-regulation of genes involved in DCs activation pathway. Furthermore, TNF-α inhibition upon collagen Istimulation up-regulated the expression of interferon regulatory transcription factor IRF4, when compared to collagen I only treated cells. Collectively, our data demonstrate that collagen I induce TNF-α production, which is crucial for the activation and function of DCs, through down-regulation of IRF4, and implicates the importance in development of anti- TNF-α therapeutics for several inflammatory diseases.
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