Resistin-like molecule β (RELMβ/FIZZ2) is highly expressed in the ileum of SAMP1/YitFc mice and is associated with initiation of ileitis

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 beta (RELM beta) 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 RELM beta in the initiation of ileal inflammation in SAMP1/Fc mice. RELM beta was highly induced in the ilea of SAMP1/Fc mice beginning at age 5 wk, coincident with the histological appearance of inflammation. RELM beta was found in ileal goblet cells and some intermediate and Paneth cells. Surprisingly, RELM beta 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. Illeitis was observed in germfree SAMPI/Fc mice, although it was attenuated relative to specific pathogen-free SAMP1/Fc mice. These data suggest that neither the early induction of RELM beta expression nor ileal inflammation requires the presence of viable intestinal flora. Neither was the induction of RELM beta dependent on the major Th1 or Th2 cytokines. However, RELM beta stimulated naive bone marrow-derived macrophages to secrete significant amounts of TNF-alpha, IL-6, and RANTES. Our data suggest that RELM beta is involved in the initiation of ileitis in SAMPI/Fc mice and may act through the induction of pro-inflammatory cytokines from resident immune cells within the mucosa.