Murakami Yousuke, Kohsaka Hitoshi
Dearptment of Medicine and Rheumatology, Graduate school of Medicine, Tokyo Medical and Dental University.
Nihon Rinsho Meneki Gakkai Kaishi. 2009 Aug;32(4):242-8. doi: 10.2177/jsci.32.242.
Triggering receptor expressed on myeloid cells (TREM)-1 is inducible on monocyte/macrophages and neutrophils and accelerates tissue destruction by propagating inflammatory responses in diseases related to bacterial infection. Its blockade suppressed fatal immune responses in mice models of sepsis without impairing the host defense. However, the influence of TREM-1 on non-bacterial diseases was not elucidated. We describe here that TREM-1 expression was up-regulated by prostaglandin (PG) E(2) as well as lipopolysaccharide. Activation of TREM-1 expressed on PGE(2)-pretreated peripheral blood mononuclear cells by an agonistic TREM-1 mAb significantly enhanced the production of TNFalpha. Indeed, monosodium urate monohydrate (MSU) crystals induced TREM-1 expression in vitro and in vivo. MSU crystals and an anti-TREM-1 agonistic antibody synergistically increased the production of interleukin-1beta compared with stimulation with the crystals alone. Furthermore, TREM-1 was expressed on CD14+ cells in rheumatoid synovial tissue and synovial macrophages from mice with collagen-induced arthritis (CIA). Blockade of TREM-1 ameliorated CIA without affecting T cell and B cell immune responses to the inducing antigen. These results provide evidence that TREM-1 may contribute the development of non-microbial inflammatory diseases through the enhancement of inflammatory responses.
髓样细胞表达的触发受体（TREM）-1在单核细胞/巨噬细胞和中性粒细胞上可被诱导表达，并通过在细菌感染相关疾病中传播炎症反应来加速组织破坏。在脓毒症小鼠模型中，阻断TREM-1可抑制致命的免疫反应，而不损害宿主防御功能。然而，TREM-1对非细菌性疾病的影响尚未阐明。我们在此描述，TREM-1的表达可被前列腺素（PG）E2以及脂多糖上调。用TREM-1激动性单克隆抗体激活在PGE2预处理的外周血单核细胞上表达的TREM-1，可显著增强TNFα的产生。实际上，单水尿酸钠（MSU）晶体在体外和体内均可诱导TREM-1表达。与单独用晶体刺激相比，MSU晶体和抗TREM-1激动性抗体可协同增加白细胞介素-1β的产生。此外，在胶原诱导性关节炎（CIA）小鼠的类风湿滑膜组织和滑膜巨噬细胞中的CD14+细胞上表达TREM-1。阻断TREM-1可改善CIA，而不影响T细胞和B细胞对诱导抗原的免疫反应。这些结果提供了证据，表明TREM-1可能通过增强炎症反应而促进非微生物炎性疾病的发展。
