Transcriptional mechanisms for induction of 5-HT1A receptor mRNA and protein in activated B and T lymphocytes

Serotonin (5-HT) up-regulates B and T lymphocyte proliferation by activating mitogen-induced cell surface 5-HT1A receptors. The mechanism of 5-HT1A receptor induction by B and T cell mitogens at the mRNA and protein levels in mouse splenocytes was addressed. Quantitation by RNase protection assay showed maximal increases of 3.4-, 3.0-, 3.8-, and 4.9-fold in relative 5-HT1A mRNA levels after 48 h of stimulation of splenocytes with Lipopolysaccharide, phytohemagglutinin, concanavalin A, or phorbol la-myristate 13-acetate plus ionomycin, respectively as compared with unstimulated cells. Mitogens did not alter 5-HT1A mRNA stability (t(1/2) = 26 h), but induction of 5-HT1A mRNA was blocked by the transcriptional inhibitor actinomycin D (10 mug/ml) and by inhibition of nuclear factor-kappaB signaling. Additionally, mitogenic stimulation of transcription was paralleled by increased cell surface 5-HT1A receptor immunoreactivity in splenocytes. Thus, mitogen-induced 5-HT, receptor expression appears to involve transcriptional regulation by the nuclear factor-kappaB signaling cascade. Increased expression of the 5-HT1A receptor in activated B and T lymphocytes may enhance the immune response and provide therapeutic target for tissue inflammation and immune stimulation.