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.
Department of Immunology and Institute of Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Korea.
Barun
B
Poudel
Hyeon-Hui
HH
Ki
Young-Mi
YM
Lee
Dae-Ki
DK
Kim
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D024042:Collagen Type I / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D050835:Interferon Regulatory Factors / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000378:metabolism*; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation; D000099218:Interferon Regulatory Factor-4
D024042:Collagen Type I; D050835:Interferon Regulatory Factors; D018664:Interleukin-12; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000099218:Interferon Regulatory Factor-4; C587672:IL1B protein, mouse