Induction and expression of beta-calcitonin gene-related peptide in rat T lymphocytes and its significance.
Our previous data have shown that rat lymphocytes can synthesize calcitonin gene-related peptide (CGRP), a neuropeptide. In this study the type, characteristics, and functional role of lymphocyte-derived CGRP were investigated. The results showed that treatment with Con A (4 microg/ml) and recombinant human IL-2 (rhIL-2; 750 U/ml) for 3-5 days induced CGRP synthesis and secretion by lymphocytes from both thymus and mesenteric lymph nodes in a time-dependent manner. Stimulation of these cells with Con A (1-8 microg/ml) or rhIL-2 (94-1500 U/ml) for 5 days induced a significant increase in CGRP secretion in a concentration-dependent manner. The maximal secretion of CGRP with Con A by thymocytes was elevated from 104+/-11 to 381 +/- 44 pg/10(8) cells, and that by mesenteric lymph node lymphocytes was elevated from 83+/-10 to 349+/-25 pg/10(8) cells, respectively. The maximal CGRP secretion with rhIL-2 by thymocytes was elevated from 116+/-3 to 607+/-23 pg/10(8), and that by mesenteric lymph node lymphocytes was elevated from 117+/-9 to 704+/- 37 pg/10(8) cells, respectively. The nucleotide sequencing study showed that lymphoid cells expressed beta-CGRP cDNA only. The levels of beta-CGRP mRNA in mitogen-stimulated lymphocytes of both sources were also increased. However, LPS had no such effect on either source of cells. hCGRP(8-37) (2.0 microM), a CGRP(1) receptor antagonist, enhanced Con A-induced proliferation and IL-2 release of thymocytes by 41.3 and 35.8% over those induced by Con A alone, respectively. The data suggest that T lymphocyte mitogens can induce the production of endogenous beta-CGRP from T lymphocytes, which may partially inhibit the proliferation and IL-2 release of rat T lymphocyte under immune challenges.
Xing
L
L
Institute of Vascular Medicine, The Third Hospital, Beijing Medical University, Beijing, People's Republic of China.
Guo
J
J
Wang
X
X
D000818:Animals; D001483:Base Sequence; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D007376:Interleukin-2; D012333:RNA, Messenger; D003208:Concanavalin A; D015740:Calcitonin Gene-Related Peptide