Somatostatin increases mitogen-induced IL-2 secretion and proliferation of human Jurkat T cells via sst3 receptor isotype.
The neuropeptide somatostatin (SRIF) modulates normal and leukemia T cell proliferation. However, neither molecular isotypes of receptors nor mechanisms involved in these somatostatin actions have been elucidated as yet. Here we show by using RT-PCR approach that mitogen-activated leukemia T cells (Jurkat) express mRNA for a single somatostatin receptor, sst3. This mRNA is apparently translated into protein since specific somatostatin binding sites (K11 = 78 +/- 3 pM) were detected in semipurified plasma membrane preparations by using 125I-Tyr1-SRIF14 as a radioligand. Moreover, somatostatin inhibits adenylyl cyclase activity with similar efficiency (IC50 = 23 +/- 4 pM) thus strongly suggesting a functional coupling of sst3 receptor to this transduction pathway. The involvement of sst3 receptor in immuno-modulatory actions of somatostatin was assessed by analysis of neuropeptide effects on IL-2 secretion and on proliferation of mitogen-activated Jurkat cells. Our data show that in the concentrations comprised between 10 pM and 10 nM, somatostatin potentiates IL-2 secretion. This effect is correlated with somatostatin-dependent increase of Jurkat cell proliferation since the EC50 concentrations for both actions were almost identical (EC50 = 22 +/- 9 pM and EC50 = 12 +/- 1 pM for IL-2 secretion and proliferation, respectively). Altogether, these data strongly suggest that in mitogen-activated Jurkat cells, somatostatin increases cell proliferation through the increase of IL-2 secretion via a functional sst3 receptor negatively coupled to the adenylyl cyclase pathway.
Cardoso
A
A
Laboratoire de Biologie Moléculaire et Cellulaire, Lyon, France.
el Ghamrawy
C
C
Gautron
J P
JP
Horvat
B
B
Gautier
N
N
Enjalbert
A
A
Krantic
S
S
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000235:genetics / Q000502:physiology; D007376:Interleukin-2 / Q000378:metabolism*; D007457:Iodine Radioisotopes; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens / Q000494:pharmacology; D011485:Protein Binding; D017481:Receptors, Somatostatin / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D013004:Somatostatin / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*
D007132:Immunoglobulin Isotypes; D007376:Interleukin-2; D007457:Iodine Radioisotopes; D008934:Mitogens; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; D013004:Somatostatin; D000262:Adenylyl Cyclases