Induction of proinflammatory cytokines and caspase-1 by leptin in monocyte/macrophages from Holstein cows
Induction of proinflammatory cytokines and caspase-1 by leptin in monocyte/macrophages from Holstein cows
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DOI：
10.1292/jvms.69.509
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发表时间：
2007-05-01
影响因子：
1.2
通讯作者：
Kimura, Kazuhiro
中科院分区：
文献类型：
--
作者：
Ahmed, Mohamed;Shaban, Zein;Kimura, Kazuhiro
含有单核/巨噬细胞和T淋巴细胞的外周血单个核细胞（PBMC）的增殖增加后，与T细胞有丝分裂原（刀豆球蛋白A：Con A）处理。与单独用ConA处理的PBMC相比，单独用瘦素或瘦素和ConA的组合处理的PBMC显示出10- 40%的增殖活性增强。与此相反，与单独的ConA处理的瘦素和分离的T淋巴细胞显示出较低的增殖活性，表明瘦素诱导的单核细胞/巨噬细胞的一些细胞因子的产生，随后导致在PBMC中的T淋巴细胞增殖的增强。在检测的细胞因子中，单核细胞/单核细胞组成性表达白细胞介素（IL）-1 β、IL-12 p35、IL-18 mRNA，微弱表达肿瘤坏死因子（TNF）-α和IL-12 p40 mRNA。瘦素处理增加单核细胞/巨噬细胞的mRNA表达，只有TNF-α和IL-12 p40的细胞用脂多糖（LPS）处理的水平相当。然而，瘦素处理增加单核细胞/巨噬细胞产生IL-1 β以及TNF-α，并诱导半胱天冬酶-1的mRNA表达，其显示介导潜伏的pro-IL-1 β和pro-IL-18转化为活性形式。这些结果表明，瘦素直接作用于单核细胞/巨噬细胞以产生诱导T淋巴细胞增殖的因子，例如通过IL 12 p40诱导的IL-12 p35/p40复合物和通过半胱天冬酶-1诱导的IL-1 β/IL-18产生。
The proliferation of peripheral blood mononuclear cells (PBMC) containing both monocyte/macrophages and T lymphocytes increased after treatment with T-cell mitogen (concanavalin A: Con A). PBMC treated with either leptin alone or combination of leptin and ConA showed enhanced proliferative activity by 10-40%, compared with those treated with ConA alone. In contrast, isolated T lymphocytes treated with leptin and ConA showed lowered proliferative activity than the ConA-treated alone, indicating that leptin induced production of some cytokines from monocyte/macrophages, that subsequently resulted in enhancement of T lymphocytes proliferation in PBMC. Among the cytokines examined, monocyte/monocytes constitutively expressed interleukin (IL)-1 beta, IL-12p35, IL-18 mRNA, and faintly expressed tumor necrosis factor (TNF)-alpha and IL-12p40 mRNA. Leptin treatment augmented the monocyte/macrophages mRNA expression of only TNF-alpha and IL-12p40 to comparable levels of cells treated with lipopolysaccharide (LPS). However, leptin treatment increased monocyte/macrophages production of IL-1 beta as well as TNF-alpha, and induced the mRNA expression of caspase-1, which is shown to mediate the conversion of latent pro-IL-1 beta and pro-IL-18 to active forms. These results suggest that leptin directly acts on monocyte/macrophages to produce factors that induce T lymphocytes proliferation such as IL-12p35/p40 complex through IL12p40 induction and IL-1 beta/IL-18 production through caspase-1 induction.