Differential effect of serotonin on cytokine production in lipopolysaccharide-stimulated human peripheral blood mononuclear cells:: involvement of 5-hydroxytryptamine2A receptors

Differential effect of serotonin on cytokine production in lipopolysaccharide-stimulated human peripheral blood mononuclear cells:: involvement of 5-hydroxytryptamine2A receptors
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DOI:
10.1093/intimm/dxg027
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发表时间:
2003-02-01
影响因子:
4.4
通讯作者:
Cavaillon, JM
Cavaillon, JM
中科院分区:
医学3区
文献类型:
--
作者:
Cloëz-Tayarani, I;Petit-Bertron, AF;Cavaillon, JM

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为了进一步了解血清素[5-羟色胺(5-HT)]在炎症中的体内意义,我们研究了其对脂多糖(LPS)刺激的人外周血单核细胞(PBMC)中肿瘤坏死因子(TNF)-α、IL-1 α、IL-β、IL-6、IL-10和IL-1受体拮抗剂产生的影响。5-HT抑制PBMC中TNF-α的产生并增加IL-1 β的产生。IL-1 β转化酶/caspase-1水平保持不变,表明5-HT的作用与IL-1 β成熟过程没有直接关系。TNF-α mRNA和IL-1 β mRNA的含量在5-HT存在下没有变化。5-HT对所研究的其他细胞因子的产生没有任何影响。5-HT对TNF-α产生的抑制作用被选择性5-HT 2A拮抗剂酮色林拮抗,并被选择性5-HT 2A/2C激动剂DOI模拟。这些发现表明,5-HT对TNF-α产生的抑制涉及PBMC中5-HT 2A受体亚型的参与。因此,我们通过Western印迹分析检测PBMC中5-HT 2A受体的存在。我们的数据支持5-HT通过其对PBMC中细胞因子产生的影响在炎症中的作用。
In order to provide additional insight into the in vivo significance of serotonin [5-hydroxytryptamine (5-HT)] in inflammation, we examined its effect on the production of tumor necrosis factor (TNF)-alpha, IL-1alpha, IL-beta, IL-6, IL-10 and IL-1 receptor antagonist in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMC). 5-HT inhibited TNF-alpha production and increased IL-1beta production in PBMC. The level of IL-1beta-converting enzyme/caspase-1 remained unchanged, suggesting that the effect of 5-HT is not directly related to the IL-1beta maturation process. TNF-alpha mRNA and IL-1beta mRNA content did not change in the presence of 5-HT. 5-HT did not have any effect on the production of other cytokines studied. The inhibitory effect of 5-HT on TNF-alpha production was antagonized by ketanserin, a selective 5-HT2A antagonist, and mimicked by DOI, a selective 5-HT2A/2C agonist. These findings suggest that the inhibition of TNF-alpha production by 5-HT involves the participation of the 5-HT2A receptor subtypes in PBMC. Accordingly, we detected the presence of 5-HT2A receptors in PBMC by Western blot analysis. Our data support a role of 5-HT in inflammation through its effect on cytokine production in PBMC.