Differential effect of serotonin on cytokine production in lipopolysaccharide-stimulated human peripheral blood mononuclear cells: involvement of 5-hydroxytryptamine2A receptors.
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-1beta, 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-HT(2A) antagonist, and mimicked by DOI, a selective 5-HT(2A/2C) agonist. These findings suggest that the inhibition of TNF-alpha production by 5-HT involves the participation of the 5-HT(2A) receptor subtypes in PBMC. Accordingly, we detected the presence of 5-HT(2A) 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.
Cloëz-Tayarani
Isabelle
I
UP Cytokines & Inflammation, Institut Pasteur, 25-28 rue du Dr Roux, 75015 Paris, France. icloez@pasteur.fr
Petit-Bertron
Anne-France
AF
Venters
Homer D
HD
Cavaillon
Jean-Marc
JM
D016207:Cytokines / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*
D016207:Cytokines; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D011985:Receptors, Serotonin; D012701:Serotonin