Collagen I-induced dendritic cells activation is regulated by TNF-[alpha] production through down-regulation of IRF4

Previously we have shown that collagen I enhances the maturation and function of dendritic cells (DCs). Inflammatory mediators such as tumour necrosis factor (TNF)-[alpha], interleukin (IL)-1[beta] and lipopolysaccharide (LPS) are also known to activate DCs. Here we investigated the involvement of TNF-[alpha] 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-[alpha] 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-[alpha] 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-[alpha] therapeutics for several inflammatory diseases.