Importance of Histamine in the Cytokine Network in the Lung Through H2 and H3 Receptors: Stimulation of IL-10 Production1
Importance of Histamine in the Cytokine Network in the Lung Through H2 and H3 Receptors: Stimulation of IL-10 Production1
复制标题
组胺通过 H2 和 H3 受体在肺部细胞因子网络中的重要性：刺激 IL-10 的产生1
作者：
J. Sirois;G. Ménard;A. Moses;É. Bissonnette
组胺是一种众所周知的炎症介质，它与各种免疫调节作用有关，但目前还不清楚。因此，我们测试了组胺通过刺激抗炎细胞因子IL-10的释放来抑制促炎细胞因子即TNF的释放的假设。将来自人、Sprague道利大鼠和AM细胞系NR 8383的肺泡巨噬细胞（AM）用不同浓度的组胺（10−5-10−7 M）处理2 h，然后用次优浓度的LPS（1 ng/ml）刺激4 h。组胺以剂量依赖性方式抑制TNF释放。H2和H3受体激动剂可模拟这种抑制作用，但H1受体激动剂不能模拟这种抑制作用。此外，我们证明了H3受体mRNA在人类AM中的表达。有趣的是，在加入组胺之前用抗IL-10、抗PGE 2或NO合酶抑制剂（Nω-硝基-l-精氨酸甲酯）处理AM，消除了后者对TNF释放的抑制作用。组胺处理（10 - 5 M）增加了未刺激（2.2倍）和LPS刺激（1.7倍）AM的IL-10释放。未受刺激的AM，NR 8383，表达IL-10 mRNA的几个拷贝，通过定量PCR测试，但IL-10的表达增加了1.5倍组胺治疗。此外，用抗PGE 2或NO合酶抑制剂Nω-硝基-L-精氨酸甲酯预处理可消除组胺对IL-10释放的刺激。因此，组胺通过PGE 2和NO的产生增加AM合成和释放IL-10。这些结果表明，组胺可能在细胞因子网络的调制中发挥重要作用。
Histamine, a well-known inflammatory mediator, has been implicated in various immunoregulatory effects that are poorly understood. Thus, we tested the hypothesis that histamine inhibits the release of a proinflammatory cytokine, namely TNF, by stimulating the release of an anti-inflammatory cytokine, IL-10. Alveolar macrophages (AMs) from humans, Sprague Dawley rats, and the AM cell line, NR8383, were treated with different concentrations of histamine (10−5-10−7 M) for 2 h prior to their stimulation with suboptimal concentration of LPS (1 ng/ml) for 4 h. Histamine inhibited TNF release in a dose-dependent manner. This inhibition was mimicked by H2 and H3 receptor agonists, but not by H1 receptor agonist. Furthermore, we demonstrated the expression of H3 receptor mRNA in human AMs. Interestingly, treatment of AMs with anti-IL-10, anti-PGE2, or a NO synthase inhibitor (Nω-nitro-l-arginine methyl ester) before the addition of histamine abrogated the inhibitory effect of the latter on TNF release. Histamine treatment (10−5 M) increased the release of IL-10 from unstimulated (2.2-fold) and LPS-stimulated (1.7-fold) AMs. Unstimulated AMs, NR8383, express few copies of IL-10 mRNA, as tested by quantitative PCR, but expression of IL-10 was increased by 1.5-fold with histamine treatment. Moreover, the stimulation of IL-10 release by histamine was abrogated by pretreatment with anti-PGE2 or the NO synthase inhibitor, Nω-nitro-l-arginine methyl ester. Thus, histamine increases the synthesis and release of IL-10 from AMs through PGE2 and NO production. These results suggest that histamine may play an important role in the modulation of the cytokine network.
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DOI：
10.1016/0167-4889(88)90106-1
发表时间：
1988
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Malinowska,DH;Sachs,G;Cuppoletti,J
通讯作者：
Cuppoletti,J
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影响因子：
4.3
作者：
Staszak,C;Goodwin,JS
通讯作者：
Goodwin,JS
组胺和哮喘。
DOI：
10.1164/arrd.1987.135.5.1165
发表时间：
1987
期刊：
The American review of respiratory disease
影响因子：
--
作者：
White,MV;Slater,JE;Kaliner,MA
通讯作者：
Kaliner,MA
DOI：
10.1165/ajrcmb/9.4.371
发表时间：
1993-10-01
影响因子：
6.4
作者：
KOBZIK, L;BREDT, DS;STAMLER, JS
通讯作者：
STAMLER, JS