Severe pancreatitis with exocrine destruction and increased islet neogenesis in mice with suppressor of cytokine signaling-1 deficiency
- Author(s)
- Chen, Y; Chong, MMW; Darwiche, R; Thomas, HE; Kay, TWH;
- Details
- Publication Year 2004-09,Volume 165,Issue #3,Page 913-921
- Journal Title
- AMERICAN JOURNAL OF PATHOLOGY
- Publication Type
- Journal Article
- Abstract
- Mice with suppressor of cytokine signaling-1 (SOCS-1) deficiency die within 3 weeks of birth from a multiorgan inflammatory disease. Increased systemic levels and sensitivity of cells to the inflammatory cytokines interferon-gamma and tumor necrosis factor may contribute to the disease. Hepatitis and liver failure are thought to be the cause of die neonatal lethality in these mice. Here, we show that die pancreata of SOCS-1(-/-) mice are also severely affected by inflammation, displaying extensive edema and infiltration by T cells and macrophages. Acinar cells in particular were atrophied and reduced in their zymogen content The expression of inflammatory markers, including class I major histocompatibility complex and inducible nitric oxide synthase, were increased in the SOCS-1(-/-) pancreas. Although there was generalized up-regulation of class I major histocompatibility complex, inducible nitric oxide synthase expression was more prominent on exocrine tissues. There appeared to be preferential damage and apoptosis of exocrine over endocrine components. Unexpectedly, increased islet neogenesis, possibly from proliferating ductal cells, was observed in the pancreas of SOCS-1(-/-) mice. This is reminiscent of the pancreatitis and islet neogenesis that occur in mice that transgenically overexpress; interferon-gamma and/or tumor necrosis factor. This study suggests that in addition to liver failure, the pancreatitis may also be an important contributor to the neonatal lethality in SOCS-1(-/-) mice.
- Publisher
- AMER SOC INVESTIGATIVE PATHOLOGY, INC
- Keywords
- TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; INTERFERON-GAMMA; FACTOR-ALPHA; BETA-CELLS; TRANSGENIC MICE; TNF-ALPHA; IFN-GAMMA; NEGATIVE REGULATION; DUCT-CELL
- Publisher's Version
- https://doi.org/10.1016/S0002-9440(10)63353-6
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- Refer to copyright notice on published article.
Creation Date: 2004-09-01 12:00:00