Growth Hormone Prevents Fas-Induced Apoptosis in Lymphocytes through Modulation of Bcl-2 and Caspase-3

Abstract

Objective: Growth hormone (GH) has been reported to have a potent effect on the immune system. However, the detailed mechanism of the effect of GH on the immune system has not yet been clarified. This study was designed to investigate the nature of this mechanism. Methods: In the present study, we investigated the effects of GH on the susceptibility of both human CEM/C7 lymphocytes and human IM-9 lymphocytes to Fas-induced apoptosis. Results: Both cell lines expressed GH receptor mRNA. GH rescued Fas-induced suppression of [³H]-thymidine incorporation into each cell line. GH prevented Fas-induced apoptosis in each cell line without changing Fas antigen expression. We next investigated the mechanisms of the prevention of Fas-induced apoptosis, by focusing on intracellular molecules related to the apoptotic signal. Bcl-2 expression was increased by GH treatment in both CEM/C7 and IM-9 lymphocytes. GH also downregulated caspase-3 expression and inhibited activation of caspase-3 in both cell lines. Conclusion: These findings suggest that GH regulates the human immune system through inhibition of Fas-induced apoptosis in activated T and B lymphocytes.

Expression, regulation and biological actions of growth hormone (GH) and ghrelin in the immune system

“…Matsuda et al reported that GH down-regulated Fas expression on human neutrophils and inhibited the apoptosis [117]. Human GH reportedly diminished Fas-mediated cell death without changing Fas antigen by enhancing the expression of the anti-apoptotic oncoprotein Bcl-2 and depressing Fas-induced activation of the cysteine protease, caspase-3, using human T and B lymphocyte cell lines, promonocytic cell line, and human primary cultured monocytes [118,119]. GH protected human lymphocytes from irradiation-induced cell death by increasing Bcl-2 [120].…”

Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network

“…Pankov [62] reviewed these and other studies that showed that lymphoid tissues including the spleen, thymus, lymph nodes and peripheral blood cells expressed GH, GHR and IGF-1, the downstream effector of GH. Thus, GH and PRL can act directly on hematopoietic cells including lymphocytes to mediate effects such as enhanced proliferation [63] [64] and/or inhibition of apoptosis, e.g., [65], [66], [67], [68].…”

Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair

“…Fas expression did not significantly change in the PMN from patients treated with hGH when compared with placebo-treated controls (data not shown), but hGH is known to down-regulate Fas expression in PMN in cell-culture experiments [17]. Further, rather than decreasing Fas expression, GH has been shown to prevent Fas-induced apoptosis in human leukocyte lines through an increase in BCL-2 a decrease in caspase-3 expression and activity [35].…”