| First Author | Li B | Year | 2014 |
| Journal | Mucosal Immunol | Volume | 7 |
| Issue | 4 | Pages | 869-78 |
| PubMed ID | 24301657 | Mgi Jnum | J:234754 |
| Mgi Id | MGI:5790776 | Doi | 10.1038/mi.2013.103 |
| Citation | Li B, et al. (2014) IL-10 modulates DSS-induced colitis through a macrophage-ROS-NO axis. Mucosal Immunol 7(4):869-78 |
| abstractText | Breakdown of the epithelial barrier because of toxins or other insults leads to severe colitis. Interleukin-10 (IL-10) is a critical regulator of this, yet its cellular targets and mechanisms of action are not resolved. We address this here. Mice with a macrophage-selective deletion of IL-10Ralpha (IL-10Ralpha(Mdel)) developed markedly enhanced dextran sodium sulfate (DSS)-induced colitis that did not significantly differ from disease in IL-10(-/-) or IL-10Ralpha(-/-) mice; no impact of IL-10Ralpha deficiency in other lineages was observed. IL-10Ralpha(Mdel) colitis was associated with increased mucosal barrier disruption in the setting of intact epithelial regeneration. Lamina propria macrophages (LPMphis) did not show numerical or phenotypic differences from controls, or a competitive advantage over wild-type cells. Proinflammatory cytokine production, and particularly tumor necrosis factor-alpha (TNF-alpha), was increased, although TNF-alpha neutralization failed to reveal a defining role for this cytokine in the aggravated disease. Rather, IL-10Ralpha(Mdel) LPMphis produced substantially greater levels of nitric oxide (NO) and reactive oxygen species (ROS) than controls. Inhibition of these had modest effects in wild-type mice, although they dramatically reduced colitis severity in IL-10Ralpha(Mdel) mice, and largely eliminated the differential effect of DSS in them. Therefore, the palliative actions of IL-10 in DSS-induced colitis predominantly results from its macrophage-specific effects. Downregulation of NO and ROS production are central to the protective actions of IL-10. |
