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Pancreatitis is an inflammatory disease characterized by the induction of several pro-inflammatory cytokines like interleukin (IL)-6, IL-8, IL-1β, and IL-1. Recently, a multifunctional innate cytokine IL-15 has been implicated in the protection of several diseases including cancer. Tissue fibrosis is one of the major problems to treat successfully chronic pancreatitis pathogenesis. Therefore, we tested the hypothesis that rIL-15 treatment may induce innate tissue responses and its over-expression will improve the pathogenesis of cerulein-induced chronic pancreatitis, associated remodeling and fibrosis. We observed atrophy of acinar cells, increased inflammation, and increased deposition of perivascular collagen, the up-regulated protein level of TGF-β1, α-SMA, and collagen-1 in cerulein-induced chronic pancreatitis in mice. Further, we reported that rIL-15 treatment protects mice from the cerulein-induced chronic pancreatitis pathogenesis including acinar cells atrophy, and perivascular accumulation of tissue collagen followed by down-regulation of pro-fibrotic genes such as TGF-β1, α-SMA, Collagen-1, Collagen-3, and Fibronectin in cerulein-induced chronic pancreatitis in mice. Mechanistically, we show that IL-15-mediated increase of IFN-Υ responsive iNKT cells in the blood and tissue protects cerulein-induced pancreatic pathogenesis in mice. Of note, a reduced iNKT cells were also observed in the human chronic pancreatitis compared to the normal individuals. Taken together, these data suggest that IL-15 treatment may be a novel therapeutic strategy for treating chronic pancreatitis pathogenesis.
This article was published in the following journal.
Name: American journal of physiology. Gastrointestinal and liver physiology
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Acute or chronic INFLAMMATION of the PANCREAS due to excessive ALCOHOL DRINKING. Alcoholic pancreatitis usually presents as an acute episode but it is a chronic progressive disease in alcoholics.
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