Regulation of apoptosis by somatostatin and substance P in peritoneal macrophages

Recent studies have shown that somatostatin (SOM) inhibits interleukin 6 (I L-6) and interferon gamma (IFN-gamma) production by lymphocytes and periton eal macrophages, whereas substance P (SP) enhances these cytokines producti on. To define the mechanism of the cytokine production enhancements and inh ibitions by SOM and SP, we examined the expression of apoptosis modulator, p53, Bcl-2, Bax, inducible nitric oxide synthase (iNOS). Fas, caspase-8 and nitric oxide (NO) in thioglycolate-elicited peritoneal macrophages. SOM ca used up-regulation of p53, Bcl-2, Fas and caspase-8 activities, and down-re gulation of iNOS expression and NO production. On the other hand, SP slight ly induces p53 and highly induces Bcl-2, iNOS expression and NO production. These data suggest that apoptosis by SOM may occur by a Bax- and NO-indepe ndent p53 accumulation, and through Fas and caspase-8 activation pathways, and that the inducible expression of Bcl-2 and NO production by SP may cont ribute to prevent the signals of apoptosis by Bax, and via Fas and caspase- 8 activation. (C) 2001 Elsevier Science B.V. All rights reserved.