Receptor activator of NF-κB ligand and osteoprotegerin regulate proinflammatory cytokine production in mice

Kenta Maruyama, Yasunari Takada, Neelanjan Ray, Yukiko Kishimoto, Josef M. Penninger, Hisataka Yasuda, Koichi Matsuo

研究成果: Article査読

73 被引用数 (Scopus)

抄録

Receptor activator of NF-κB; ligand (RANKL) is a membrane-bound or soluble cytokine essential for osteoclast differentiation, whereas the decoy receptor osteoprotegerin (OPG) masks RANKL activity. In mouse serum, both soluble RANKL and OPG are detectable. We observed that mice injected with LPS showed significantly down-regulated serum RANKL levels, whereas serum OPG levels were up-regulated. However, the roles of RANKL and OPG in innate immunity remain obscure. We found that RANKL pretreatment suppressed production of proinflammatory cytokines in macrophages in response to stimulation by bacteria and their components. Furthermore, such RANKL-induced tolerance in macrophages was inhibited by GM-CSF treatment, which blocks RANKL signaling. RANKL-induced tolerance occurred in the absence of c-Fos, which is essential for osteoclast differentiation. In mice lacking OPG, LPS-induced production of proinflammatory cytokines was reduced, whereas in mice lacking RANKL, it was increased, and lethality following LPS injection was also elevated, suggesting that constitutive activities of RANKL suppress cytokine responsiveness to LPS in vivo. Strikingly, prior administration of RANKL protected mice from LPS-induced death. These data reveal prophylactic potential of RANKL in acute inflammatory diseases.

本文言語English
ページ(範囲)3799-3805
ページ数7
ジャーナルJournal of Immunology
177
6
DOI
出版ステータスPublished - 2006 9 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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