Article Text

other Versions

Expression of Interleukin-1-like Cytokine Interleukin-33 and its Receptor Complex (ST2L and IL-1RAcP) in Human Pancreatic Myofibroblasts.
  1. Atsushi Nishida1,
  2. Akira Andoh1,*,
  4. Testuya Sugihara2,
  5. Osamu Inatomi1,
  6. Hisanori Shiomi1,
  7. Yoshihide Fujiyama1
  1. 1 Shiga University of medical Science, Japan;
  2. 2 Shiga University of Medical Science, Japan
  1. Correspondence to: AKIRA ANDOH, SHIGA UNIVERSITY OF MEDICAL SCIENCE, Department of Internal Medicine, Shiga Universisy of Medical Science, Otsu, 520-2192, Japan; andoh{at}


Objective: Interleukin (IL)-33 is a cytokine belonging to the IL-1 family. IL-33 binds to a complex of ST2L/IL-1 receptor accessory protein (IL-1RAcP). To define the role of IL-33 in fibrogenesis in the pancreas, the expression of IL-33, ST2L and IL-1RAcP was examined in chronic pancreatitis tissues. The effects of IL-33 on the functions of human pancreatic myofibroblasts were also investigated.

Methods: Tissue samples were obtained surgically. The expression of IL-33, ST2L and IL-1RAcP was evaluated by standard immunohistochemical procedures. Messenger RNA expression for IL-33, ST2L and IL-1RAcP was analyzed by Northern blotting and real-time PCR analyses, and protein expression was assessed by Western blotting and ELISA. Cell proliferation and migration were assessed by a [3H]thymidine incorporation assay and the modified Boyden chamber assay, respectively.

Results: IL-33, ST2L and IL-1RAcP were expressed by α-SMA-positive myofibroblasts in the fibrosis of chronic pancreatitis. In human pancreatic myofibroblasts, IL-33 was weakly immunoexpressed without any stimuli, and this was markedly enhanced by IL-1β], TNF-α\ and lipopolysaccharide (LPS) via the mitogen-activated protein kinase (MAPK)-dependent AP-1 activation pathway. ST2L mRNA was weakly detected in un-stimulated cells, and IL-4 and IFN-γ strongly enhanced ST2L expression via STAT6- and STAT1 signaling, respectively. IL-33 rapidly induced the phosphorylation of MAPKs and IκBα, and enhanced the expression of inflammatory mediators (IL-6, IL-8, IP-10, Gro-α, Gro-β and MCP-1) in IL-4- or IFN-γ-pretreated cells. IL-33 stimulated the proliferation and migration of pancreatic myofibroblasts.

Conclusions: IL-33 and its receptor complex (ST2L and IL-1RAcP) are a novel signaling system which may play an important role in the pathogenesis of chronic pancreatitis.

Statistics from


    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.