Serotonin mediates PGE₂ overexpression through 5-HT_2A and 5-HT₃ receptor subtypes in serum-free tissue culture of macrophage-like synovial cells

摘要

Serotonin antagonists show impressive analgesic efficacy in rheumatoid arthritis, osteoarthritis (OA) or fibromyalgia; however, this effect is not well understood. We examined the mechanism of serotonin-induced inflammation and its antagonists in OA. Serotonin receptor subtypes and COX-2 were analysed by RT-PCR from synovial tissue. Serum-free cultures were stimulated with 10 μM serotonin and/or the antagonists ketanserin (5-HT_2A), tropisetron (5-HT₃) and parecoxib (COX-2). Prostaglandin E₂ (PGE₂), tumour necrosis factor alpha (TNF-α), interleukin 1β (IL-1β) and leukotriene B4 (LTB4) were measured by an immunoassay in the supernatants. RT-PCR results showed mRNA for 5-HT_2A and 5-HT₃ receptors, and COX-2. PGE₂ in the supernatants increased by 261.2% ± 56.7 (mean ± SEM; P = 0.007) in response to serotonin. TNF-α, IL-1β and LTB4 levels did not change. Ketanserin, tropisetron and parecoxib suppressed PGE₂. The serotonin-induced PGE₂ overexpression appeared thus to be mediated by 5-HT_2A and 5-HT₃ receptors. This activation might involve COX-2. The findings may explain the potent benefit of 5-HT₃ antagonists.