旁分泌 IL-33 刺激增强脂多糖介导的巨噬细胞活化。
Paracrine IL-33 stimulation enhances lipopolysaccharide-mediated macrophage activation.
机构信息
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
出版信息
PLoS One. 2011 Apr 11;6(4):e18404. doi: 10.1371/journal.pone.0018404.
BACKGROUND
IL-33, a member of the IL-1 family of cytokines, provokes Th2-type inflammation accompanied by accumulation of eosinophils through IL-33R, which consists of ST2 and IL-1RAcP. We previously demonstrated that macrophages produce IL-33 in response to LPS. Some immune responses were shown to differ between ST2-deficient mice and soluble ST2-Fc fusion protein-treated mice. Even in anti-ST2 antibody (Ab)-treated mice, the phenotypes differed between distinct Ab clones, because the characterization of such Abs (i.e., depletion, agonistic or blocking Abs) was unclear in some cases.
METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the precise role of IL-33, we newly generated neutralizing monoclonal Abs for IL-33. Exogenous IL-33 potentiated LPS-mediated cytokine production by macrophages. That LPS-mediated cytokine production by macrophages was suppressed by inhibition of endogenous IL-33 by the anti-IL-33 neutralizing mAbs.
CONCLUSIONS/SIGNIFICANCE: Our findings suggest that LPS-mediated macrophage activation is accelerated by macrophage-derived paracrine IL-33 stimulation.
背景
IL-33 是白细胞介素-1 家族细胞因子的成员，通过由 ST2 和 IL-1RAcP 组成的 IL-33R 引发 Th2 型炎症，伴随嗜酸性粒细胞的积累。我们之前证明巨噬细胞在 LPS 刺激下产生 IL-33。一些免疫反应在 ST2 缺陷小鼠和可溶性 ST2-Fc 融合蛋白处理的小鼠之间存在差异。即使在抗 ST2 抗体（Ab）处理的小鼠中，不同 Ab 克隆的表型也存在差异，因为在某些情况下，这些 Ab 的特性（即耗竭、激动或阻断 Ab）尚不清楚。
方法/主要发现：为了阐明 IL-33 的精确作用，我们新生成了针对 IL-33 的中和单克隆抗体。外源性 IL-33 增强了 LPS 介导的巨噬细胞细胞因子的产生。抗 IL-33 中和单克隆抗体抑制内源性 IL-33 可抑制 LPS 介导的巨噬细胞细胞因子的产生。
结论/意义：我们的研究结果表明，LPS 介导的巨噬细胞激活是通过巨噬细胞衍生的旁分泌 IL-33 刺激加速的。
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