MECHANISM OF SUPPRESSION OF NITRIC-OXIDE SYNTHASE EXPRESSION BY INTERLEUKIN-4 IN PRIMARY MOUSE MACROPHAGES
MECHANISM OF SUPPRESSION OF NITRIC-OXIDE SYNTHASE EXPRESSION BY INTERLEUKIN-4 IN PRIMARY MOUSE MACROPHAGES
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DOI：
10.1002/jlb.55.2.227
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发表时间：
1994-02-01
影响因子：
5.5
通讯作者：
NATHAN, C
中科院分区：
文献类型：
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作者：
BOGDAN, C;VODOVOTZ, Y;NATHAN, C
一氧化氮 (NO) 有助于巨噬细胞的抗肿瘤、抗菌和免疫抑制活性。诱导型一氧化氮合酶 (iNOS) 负责巨噬细胞在受到细胞因子和/或脂多糖 (LPS) 刺激后大量产生一氧化氮。在本研究中，我们证明白细胞介素 4 (IL-4) 可以抑制暴露于 IFN-γ（有或没有 LPS）的原代小鼠腹膜巨噬细胞产生 NO，即使在协同 IFN-γ 增加 TNF-α 的分泌时也是如此。 NO 产生的抑制与 iNOS 酶活性和 iNOS 抗原的降低同时发生。暴露于 IFN-γ 后 4-6 小时，IL-4 不会抑制 iNOS mRNA 的诱导，但在刺激后期（24-72 小时）强烈减少 iNOS mRNA，而不增加其周转率。 IL-4最大程度抑制iNOS表达的条件和抑制机制与其他地方描述的转化生长因子β平行测定的条件不同。这些结果说明了不同细胞因子失活的巨噬细胞表型的多样性，并证明IL-4有可能降低巨噬细胞的抗肿瘤、抗菌和免疫抑制活性的一种成分。
Nitric oxide (NO) contributes to the antitumor, antimicrobial, and immunosuppressive activity of macrophages. An inducible form of NO synthase (iNOS) is responsible for high output generation of nitric oxide by macrophages after stimulation with cytokines and/or lipopolysaccharide (LPS). In the present study, we demonstrate that interleukin 4 (IL-4) suppressed production of NO by primary mouse peritoneal macrophages exposed to IFN-gamma with or without LPS, even while synergizing ith IFN-gamma to increase the secretion of TNF-alpha. Suppression of NO production was paralleled by decreases in iNOS enzyme activity and iNOS antigen. IL-4 did not inhibit induction of iNOS mRNA 4-6 h after exposure to IFN-gamma, but strongly reduced iNOS mRNA at later times of stimulation (24-72 h), without increasing its turnover. The conditions for maximal suppression of iNOS expression by IL-4 and the mechanisms of suppression differed from those determined in parallel for transforming growth-factor-beta as described elsewhere. These results illustrate the diversity of phenotypes of macrophages deactivated by different cytokines, and demonstrate that IL-4 has the potential to reduce one component of the anti-tumor, antimicrobial, and immunosuppressive activities of macrophages.