Abstract 1452: IL-15 overexpression protects cerulein-induced fibrosis in the mouse model of chronic pancreatitis

Abstract

Abstract Introduction: Earlier, interleukin (IL)-6, IL-8, IL-1β and IL-10 are implicated in the pathogenesis of pancreatitis. Recently, we observed reduced level of IL-15 in cerulein- induced acute and chronic mouse model of pancreatitis. IL-15 is a pleiotropic cytokine that has an important role in innate immunity. Therefore, we tested the hypothesis that IL-15 overexpression improves the pathogenesis of cerulein-induced pancreatitis. Experimental procedure: Accordingly, we tested our hypothesis by inducing chronic pancreatitis in rIL-15 pretreated Balb/c mice. Cerulein was given by repetitive intraperitoneal (i.p.) injections as reported earlier (50 μg/kg, 6 hourly injections/day, 3 days/week) along with the rIL-15 (5 μg in 100μl saline/ two-times/week/mice) for up to 4 weeks; the control mice received 100μl saline or saline with 5 μg IL-15. Mice were sacrificed 3 days after the last cerulein injection. Histopathological evaluation of H&E stained tissue sections was performed including tissue remodeling and the accumulation of collagen by Masson's trichrome stain in the tissue sections. Additionally, pro-inflammatory and pro-fibrotic gene i.e. TGF-β1, IL-6, IL-8, Collagen 1 and α-SMA levels were measured by ELISA, immunofluorescence, qPCR and immunoblot analysis. Summary: We report acinar cells atrophy, induced inflammatiory cells and cytokines in the pancreas of cerulein treated mice along with perivascular collagen deposition compare to saline treated mice. Interestingly, rIL-15 treated and cerulein given mice showed significantly improved morphology of acinar cells and reduced perivascular collagen. Further, we also report that protein levels of TGF-β1 and α-SMA is also reduced in the pancreas of cerulein injected and IL-15 treated mice compare to cerulein treated mice by performing western blot and immunohistochemistry. Conclusion: Our data show that IL-15 overexpression protects mice from cerulein-induced pancreatic pathogenesis including fibrosis. Taken together, rIL-15 therapy may be a novel strategy to treat pancreatic fibrosis, and may also helpful to treat pancreatic cancer patients by down-regulating tissue fibrogenesis. Funding: NIH R01 DK067255 (AM), NIH R01 AI080581 (AM), Citation Format: MURLI MANOHAR, SATHISHA UPPARAHALLI VENKATESHAIAH, CHANDRASHEKARA PUTANAPURA MAHADEVAPPA, ALOK KUMAR VERMA, ANIL MISHRA. IL-15 overexpression protects cerulein-induced fibrosis in the mouse model of chronic pancreatitis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1452.