| First Author | Munitz A | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 4 | Pages | 2357-63 |
| PubMed ID | 19201890 | Mgi Jnum | J:144784 |
| Mgi Id | MGI:3831942 | Doi | 10.4049/jimmunol.0803130 |
| Citation | Munitz A, et al. (2009) Resistin-like molecule alpha decreases glucose tolerance during intestinal inflammation. J Immunol 182(4):2357-63 |
| abstractText | Resistin-like molecule alpha (Relm-alpha) is a secreted cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-beta, and Relm-gamma. Resistin was initially defined based on its insulin resistance activity, but the family members are highly up-regulated in various inflammatory states, especially those involving intestinal inflammation. In this study, we report the role of Relm-alpha at baseline and following an experimental model of colitis. Relm-alpha was readily detected in the serum at baseline (4-5 ng/ml), and its level was regulated by energy uptake. Retnla(-/-) mice had decreased baseline circulating leptin levels, but displayed normal glucose, glucose clearance, and insulin levels. Following exposure to the oral innate trigger dextran sodium sulfate (DSS), a nonredundant proinflammatory role for Relm-alpha was uncovered as Retnla(-/-) mice were markedly protected from DSS-induced disease activity and histopathological features. Relm-alpha regulated eosinophil-directed cytokines (e.g., IL-5, CCL11/eotaxin-1, and CCL5/RANTES) and IL-17 ex vivo. Consistently, DSS-treated Retnla(-/-) mice displayed substantially decreased eosinophil accumulation and decreased phosphorylation of NF-kappaB, ERK1/2, and p38 in macrophages and eosinophils. Following DSS exposure, serum level of Relm-alpha was up-regulated, and DSS-treated Retnla(-/-) mice were markedly protected from hyperglycemia induced by glucose injection independent of changes in insulin levels. Retnla(-/-) mice were protected from increases in gut hormone serum levels of gastric inhibitory polypeptide and peptide YY that were induced following DSS treatment. These findings demonstrate a central proinflammatory role for Relm-alpha in the regulation of colonic inflammation and a novel link between colonic injury, glucose tolerance, and energy intake. |
