Serum Thymic Factor Prevents LPS‐Induced Pancreatic Cell Damage in Mice via Up‐Regulation of Bcl‐2 Expression in Pancreas

Abstract

The protective effect of synthetic serum thymic factor (FTS) nonapeptide on lipopolysaccharide (LPS)‐induced pancreatic cell damage in 10‐week‐old BALB/c male mice was investigated. Mice were divided into three groups. Group I was treated with LPS (10 μg/head; i.p.) (LPS‐treated mice). Group II was administered with FTS (50 μg/head; i.p.) 24 hr before treatment with LPS and complemented immediately before LPS injection with FTS (50 μg/head; i.p.) (FTS‐administered mice). Group III was only treated with the same volume of saline (control mice). Treatment of LPS in vivo resulted in the destruction of pancreatic acinar cells. In those cells, many apoptotic cells were detected by immunohistochemistry using an anti‐single stranded DNA antibody. Immunohistochemistry and reverse transcription‐polymerase chain reaction (RT‐PCR) revealed that LPS treatment also caused low or a lack of insulin expression in pancreatic islets. In contrast, morphological change was not seen and apoptotic cell death was suppressed in pancreatic cells of FTS‐administered mice. Moreover, insulin expression was normal in those mice. FTS administration enhanced expression of Bcl‐2 mRNA levels in pancreatic tissues and IL‐6 mRNA levels in splenocytes significantly compared with those of LPS treatment at 3 hr after LPS injection. These findings suggest that FTS prevents LPS‐induced cell damage via enhancing Bcl‐2 expression in the pancreas and systemic IL‐6 production.

In vivo treatment with a nonapeptide thymic hormone, facteur thymique serique (FTS), ameliorates chronic colitis induced by dextran sulphate sodium in mice

“…CD4 + T cells initially stimulated in the presence of IL-10 and TGF-β tend to develop into CD4 + Tr1 and Th3 cells [42]. Saito et al have reported that FTS treatment prevented LPS-induced cell damage via enhancing systemic IL-6 production [43]. We here found spontaneous production of IL-10 but not IL-6 by the LP cells was significantly enhanced in FTS-treated mice.…”

The Toll-Like Receptor Signaling Molecule Myd88 Contributes to Pancreatic Beta-Cell Homeostasis in Response to Injury

“…At higher concentrations of LPS (e.g. 5–10 µg/ml) cytotoxic effect on islets have been observed [54], [55] and in vivo are associated with sepsis-induced hypoglycemia [56]. In sum, low-dose LPS appears to promotes insulin production and release while high dose LPS leads to stress-related responses.…”

Infection, immunity and the neuroendocrine response

“…On the contrary, GCs induce apoptosis in immature thymocytes, NK cells, and cytotoxic T-lymphocytes (Migliorati et al, 1994;Herold et al, 2006, Wang et al, 2006. Zinc and thymulin can protect thymocytes from apoptosis) induced by both GCs and TNF-a (Haeryfar and Berczi, 2001;Shankar and Prasad, 1998;Mocchegiani et al, 2004Mocchegiani et al, , 2006Saitoh et al, 2004).…”