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Bone morphogenetic protein‐6 induces the expression of inducible nitric oxide synthase in macrophages
Author(s) -
Kwon Seok J.,
Lee Geun T.,
Lee JaeHo,
Kim Wun J.,
Kim Isaac Y.
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03079.x
Subject(s) - nitric oxide synthase , microbiology and biotechnology , bone morphogenetic protein , cycloheximide , bone morphogenetic protein 10 , smad , bone morphogenetic protein 2 , nitric oxide , biology , chemistry , signal transduction , bone morphogenetic protein 7 , biochemistry , endocrinology , protein biosynthesis , gene , in vitro
Summary Bone morphogenetic proteins (BMPs) are members of the transforming growth factor‐β (TGF‐β) superfamily. In the present study, we investigated the effect of BMPs on the production of inducible nitric oxide synthase (iNOS) in the murine macrophage cell line, RAW 264.7, and in mouse peritoneal macrophages. Among the BMPs, only BMP‐6 induced iNOS expression in a time‐dependent and dose‐dependent manner in both cell types. Induction of iNOS was inhibited by both cycloheximide and actinomycin D, indicating that the induction of iNOS expression by BMP‐6 requires new protein synthesis. Mechanistic studies revealed that the BMP‐6‐induced iNOS expression requires both Smads and nuclear factor‐kappa B (NF‐κB) signalling pathways. Furthermore, induction of interleukin‐1β (IL‐1β) was necessary for iNOS induction by BMP‐6. These observations suggest that BMP‐6 stimulates macrophages to produce iNOS through IL‐1β via Smad and NF‐κB signalling pathways and that BMP‐6 may be an important regulator of macrophages.