Serotonin activates human monocytes and prevents apoptosis.
Monocytes play a critical role in chronic atopic dermatitis (AD) and are the primary leukocytes that interact with activated platelets. Although activated platelets release a variety of mediators, the role of platelets in cutaneous allergic inflammation remains unclear. Serotonin (5-hydroxytryptamine, 5-HT) is one of the prototypic mediators produced by activated platelets. We examined the effect of 5-HT on the function and lifespan of human monocytes. Normal human monocytes treated with 5-HT exhibited upregulated expression of costimulatory molecules, enhanced capacity to produce cytokines following lipopolysaccharide treatment, and to stimulate allogeneic CD4+ T cells. 5-HT also attenuated the apoptosis in normal human monocytes in a dose-dependent manner. The plasma levels of 5-HT were increased in patients with AD compared with controls and correlated with the SCORAD index. 5-HT also inhibited monocyte apoptosis in these patients. 5-HT upregulated Bcl-2 and Mcl-1, and inhibited the activation of caspase-3. The effects of 5-HT on monocyte apoptosis were mediated by the 5-HT1 and/or 5-HT7 receptors. 5-HT and a 5-HT(1/6/7)-receptor agonist induced phosphorylation of extracellular signal-regulated kinase1/2 and activation of nuclear transcription factor-kappaB. These findings support that 5-HT activates monocytes and inhibits apoptosis, allowing them to remain in the tissue and contribute to chronic inflammation.
Soga
Fujiko
F
Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.
Katoh
Norito
N
Inoue
Tomoko
T
Kishimoto
Saburo
S
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000209:etiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D053222:Fas Ligand Protein / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1 / Q000502:physiology; D012701:Serotonin / Q000097:blood / Q000494:pharmacology*; D019014:fas Receptor / Q000502:physiology
D053222:Fas Ligand Protein; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D019014:fas Receptor; C104425:serotonin 7 receptor; D012701:Serotonin; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3