Discoidin domain receptor 1 mediates collagen-induced nitric oxide production in J774A.1 murine macrophages

Sang Hyun Kim, Soyoung Lee, Kyoungho Suk, Hyun Bark, Chang Duk Jun, Dae Ki Kim, Cheol Hee Choi, Teizo Yoshimura

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Nitric oxide (NO) is an important regulator of immune responses. Effects of cytokines, such as tumor necrosis factor (TNF)-α or IFN-γ, and bacterial products, such as lipopolysaccharide, on macrophage NO production have been well documented; however, the role of the extracellular matrix proteins, including collagen, in this process remains unclear. We previously reported that discoidin domain receptor 1 (DDR1), a nonintegrin collagen receptor, was expressed in human macrophages, and its activation facilitated their differentiation as well as cytokine/chemokine production. Here, we examined the role for DDR1 in collagen-induced NO production using the murine macrophage cell line J774 cells that endogenously express DDR1. Activation of J774 cells with collagen induced the expression of inducible NO synthase (iNOS) and NO production. Inhibition of DDR1, but not β1-integrins, abolished collagen-induced iNOS and NO production. Activation of J774 cells with collagen-activated nuclear factor-κB, p38 mitogen-activated protein kinase (MAPK), and c-jun N-terminal kinase (JNK) and a pharmacological inhibitor of each signaling molecule significantly reduced collagen-induced NO production. Thus, we have demonstrated, for the first time, that the interaction of DDR1 with collagen induces iNOS expression and subsequent NO synthesis in J774 cells through activation of NF-κB, p38 MAPK, and JNK and suggest that intervention of DDR1 signaling in macrophages may be useful in controlling inflammatory diseases in which NO plays a critical role.

Original languageEnglish
Pages (from-to)343-352
Number of pages10
JournalFree Radical Biology and Medicine
Volume42
Issue number3
DOIs
Publication statusPublished - Feb 1 2007
Externally publishedYes

Keywords

  • Discoidin domain receptor 1
  • Macrophages
  • Nitric oxide
  • Nuclear factor-κB
  • c-jun N-terminal kinase
  • p38 kinase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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