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* Digestive Health Center of Excellence, University of Virginia, Charlottesville, VA 22908; and
Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
SAMP1/Fc mice develop spontaneous ileitis that shares many features with human Crohn’s disease. One of the earliest features of ileitis in SAMP1/Fc mice is an increase in the number of ileal goblet and intermediate cells. Resistin-like molecule β (RELMβ) is a goblet cell-specific, cysteine-rich peptide previously shown to function as part of the innate immune response. In this study, we examined the role of expression of RELMβ in the initiation of ileal inflammation in SAMP1/Fc mice. RELMβ was highly induced in the ilea of SAMP1/Fc mice beginning at age 5 wk, coincident with the histological appearance of inflammation. RELMβ was found in ileal goblet cells and some intermediate and Paneth cells. Surprisingly, RELMβ mRNA levels were significantly increased in the ilea of 80% of germ-free SAMP1/Fc mice examined compared with specific pathogen-free AKR control mice of similar age. Ileitis was observed in germfree SAMP1/Fc mice, although it was attenuated relative to specific pathogen-free SAMP1/Fc mice. These data suggest that neither the early induction of RELMβ expression nor ileal inflammation requires the presence of viable intestinal flora. Neither was the induction of RELMβ dependent on the major Th1 or Th2 cytokines. However, RELMβ stimulated naive bone marrow-derived macrophages to secrete significant amounts of TNF-
, IL-6, and RANTES. Our data suggest that RELMβ is involved in the initiation of ileitis in SAMP1/Fc mice and may act through the induction of proinflammatory cytokines from resident immune cells within the mucosa.
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1 This work was supported by grants to S.M.C. (National Institutes of Health (NIH) R01 DK06475, P01 DK57880), F.C. (P01 DK57880, R01 DK42191, R01 DK55812), and G.D.W. (NIH R01 AI39368) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and through the Molecular Biology and Morphology Cores of the University of Virginia NIH/NIDDK Digestive Diseases Research Core Center Grant (DK50306) and University of Pennsylvania NIH/NIDDK Center Grants (DK56703). S.L.B. was also supported by an Institutional NIH Postdoctoral Fellowship (T32 DK07769) and by a UNCF-Merck Postdoctoral Science Research Fellowship. M.-L.W. was supported by NIH KO8 DK066206.
2 S.L.B. and A.V. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Steven M. Cohn, Digestive Health Center of Excellence, Box 800708, University of Virginia Health System, Charlottesville, VA 22908. E-mail address: SC6W{at}virginia.edu
4 Abbreviations used in this paper: Tff3, intestinal trefoil factor 3; RELMβ, resistin-like molecule β; FIZZ2, found in inflammatory zone 2; mFIZZ, mouse FIZZ; Muc2, mucin 2; SPF, specific pathogen-free; GF, germfree; IBD, inflammatory bowel disease; DSS, dextran sulfate sodium; PAS, periodic acid-Schiff; ARE, AU-rich element; BM, bone marrow.
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S. M. Cohn and A. Vidrich Response to Comment on "Resistin-Like Molecule {beta} (RELM {beta}/FIZZ2) Is Highly Expressed in the Ileum of SAMP1/YitFc Mice and Is Associated with Initiation of Ileitis" J. Immunol., February 15, 2008; 180(4): 2009 - 2010. [Full Text] [PDF]
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