Bacterial colonization leads to the colonic secretion of RELMβ/FIZZ2, a novel goblet cell-specific protein

Serum concentrations of resistin-like molecules β and γ are elevated in high-fat-fed and obese db/db mice, with increased production in the intestinal tract and bone marrow

“…It was demonstrated that epithelial cells throughout the crypt and surface of the colon express both RELMβ and RELMγ, while no significant staining was observed with the control antibody. The highest level of RELMβ expression was observed in goblet cells of the colon, consistent with previous reports [15,24], and RELMγ protein was also shown to be localised in goblet cells. In the bone marrow, about 30% of haematopoietic cells were stained with the anti-RELMγ antibody and these cells were myelocytes and metamyelocytes or neutrophils (data not shown), consistent with previous reports [19,20].…”

“…In this regard, a transcriptional factor may be involved in the inflammation-induced increased expression of RELMβ and RELMγ. Indeed, the promoter region of RELMβ contains a binding sequence of nuclear factor κB and signal transducer and activator of transcription 6 [24] and RELMγ is reportedly a target gene of CCAAT/ enhancer binding protein ɛ mediating the role of promyelocytic cell development [19]. Our other interesting finding was that the expression of RELMγ was unchanged in the spleen, lung and pancreas in the insulin-resistant as compared with the control mice.…”

“…Homodimerisation of RELMβ and resistin, but not RELMα, was previously reported and conserved cysteines (Cys26 of resistin and Cys25 of RELMβ) were considered to be required for disulphide bond formation [23,24]. In RELMγ, however, the corresponding cysteine is not conserved.…”

“…The data are shown as ratios to the control lean littermate values and expressed as means±SE a p<0.01 relative to control-diet-fed mice lavage fluid in experimentally induced pulmonary inflammation, but is most abundant in adipose tissues [13]. RELMβ is specifically expressed in the intestinal tract, especially abundantly in the colon [14] and has been suggested to be related to bacterial colonisation [24]. Injecting RELMβ reportedly induced insulin resistance in rats [16].…”

Absence of bacterially induced RELMβ reduces injury in the dextran sodium sulfate model of colitis

“…We have shown that RELMβ is produced specifically by intestinal goblet cells and is secreted apically into the intestinal lumen, where it exists intact in the stool of both mice and humans (6), and likely plays a role in the defense against parasitic nematode infections of the intestine (7). RELMβ expression is essentially undetectable in the colon of both germ-free immunocompetent and SCID mice but can be induced within 48 hours upon transfer to a conventional environment, demonstrating that the expression of this gene is dependent upon bacterial colonization of the gut (6). The other 2 RELM isoforms, α and γ, as well as resistin, are not induced in the colon by colonization of the intestine with commensal bacteria (8).…”