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-HT(1A) receptors. The mechanism of 5-HT(1A) 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-HT(1A) mRNA levels after 48 h of stimulation of splenocytes with lipopolysaccharide, phytohemagglutinin, concanavalin A, or phorbol 12-myristate 13-acetate plus ionomycin, respectively, as compared with unstimulated cells. Mitogens did not alter 5-HT(1A) mRNA stability (t(12) = 26 h), but induction of 5-HT(1A) mRNA was blocked by the transcriptional inhibitor actinomycin D (10 microgram/ml) and by inhibition of nuclear factor-kappaB signaling. Additionally, mitogenic stimulation of transcription was paralleled by increased cell surface 5-HT(1A) receptor immunoreactivity in splenocytes. Thus, mitogen-induced 5-HT(1A) receptor expression appears to involve transcriptional regulation by the nuclear factor-kappaB signaling cascade. Increased expression of the 5-HT(1A) receptor in activated B and T lymphocytes may enhance the immune response and provide therapeutic target for tissue inflammation and immune stimulation.
Abdouh
M
M
Human Health Research Center, INRS-Institut Armand-Frappier, Pointe-Claire, Quebec H9R 1G6, Canada.
Storring
J M
JM
Riad
M
M
Paquette
Y
Y
Albert
P R
PR
Drobetsky
E
E
Kouassi
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001483:Base Sequence; D002455:Cell Division; D017931:DNA Primers; D005260:Female; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics*; D011985:Receptors, Serotonin / Q000096:biosynthesis* / Q000235:genetics*; D044263:Receptors, Serotonin, 5-HT1; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
D017931:DNA Primers; D016328:NF-kappa B; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1