title: Induction of IL-12 production by the activation of discoidin domain receptor 2 via NF-κB and JNK pathway.
abstract: 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-κB binding activity was enhanced when the cells expressing NF-κB 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-κB, 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-κB and JNK inhibitor treatment on collagen I stimulation. In summary, DDR2 is involved in the collagen I-induced IL-12 production via NF-κB and JNK pathway.
authors.affiliation: Department of Immunology and Institute of Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: Barun
authors.initials: B
authors.lastname: Poudel
authors.forename: Hyeon-Hui
authors.initials: HH
authors.lastname: Ki
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Lee
authors.forename: Dae-Ki
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D024042:Collagen Type I / Q000502:physiology; D000070818:Discoidin Domain Receptors; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D016328:NF-kappa B; D011975:Receptors, Mitogen; D018664:Interleukin-12; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D048670:MAP Kinase Kinase 4