We investigated the mechanism involving discoidin domain receptor 2 (DDR2) mediated production of interleukin 12 (IL-12). When compared to control, collagen I upregulated the IL-12 luciferase activity on DDR2 expressing cells. Collagen I induced the phosphorylation of DDR2 and enhanced the phosphorylation of mitogen activated protein kinase (MAPK) kinases. In addition, NF-kappa B binding activity was enhanced when the cells expressing NF-kappa B reporter were exposed to collagen I. Moreover, when IL-12 reporter transfected cells were treated with biochemical inhibitors of c-Jun N-terminal kinase (JNK) and NF-kappa B, collagen-induced IL-12 promoter activity was significantly downregulated in comparison to non-treated cells. Similarly, confirmatory experiments on murine dendritic cells revealed that IL-12 promoter activity is dose dependently downregulated upon NF-kappa B and JNK inhibitor treatment on collagen I stimulation. In summary, DDR2 is involved in the collagen I-induced IL-12 production via NF-kappa B and JNK pathway. (C) 2013 Elsevier Inc. All rights reserved.