Annexin A1 regulates intestinal mucosal injury, inflammation, and repair

BA Babbin, MG Laukoetter, P Nava, S Koch… - The Journal of …, 2008 - journals.aai.org
BA Babbin, MG Laukoetter, P Nava, S Koch, WY Lee, CT Capaldo, E Peatman, EA Severson
The Journal of Immunology, 2008journals.aai.org
During mucosal inflammation, a complex array of proinflammatory and protective
mechanisms regulates inflammation and severity of injury. Secretion of anti-inflammatory
mediators is a mechanism that is critical in controlling inflammatory responses and
promoting epithelial restitution and barrier recovery. AnxA1 is a potent anti-inflammatory
protein that has been implicated to play a critical immune regulatory role in models of
inflammation. Although AnxA1 has been shown to be secreted in intestinal mucosal tissues …
Abstract
During mucosal inflammation, a complex array of proinflammatory and protective mechanisms regulates inflammation and severity of injury. Secretion of anti-inflammatory mediators is a mechanism that is critical in controlling inflammatory responses and promoting epithelial restitution and barrier recovery. AnxA1 is a potent anti-inflammatory protein that has been implicated to play a critical immune regulatory role in models of inflammation. Although AnxA1 has been shown to be secreted in intestinal mucosal tissues during inflammation, its potential role in modulating the injury/inflammatory response is not understood. In this study, we demonstrate that AnxA1-deficient animals exhibit increased susceptibility to dextran sulfate sodium (DSS)-induced colitis with greater clinical morbidity and histopathologic mucosal injury. Furthermore, impaired recovery following withdrawal of DSS administration was observed in AnxA1 (−/−) animals compared with wild-type (WT) control mice that was independent of inflammatory cell infiltration. Since AnxA1 exerts its anti-inflammatory properties through stimulation of ALX/FPRL-1, we explored the role of this receptor-ligand interaction in regulating DSS-induced colitis. Interestingly, treatment with an ALX/FPRL-1 agonist, 15-epi-lipoxin A4 reversed the enhanced sensitivity of AnxA1 (−/−) mice to DSS colitis. In contrast, 15-epi-lipoxin A4 did not significantly improve the severity of disease in WT animals. Additionally, differential expression of ALX/FPLR-1 in control and DSS-treated WT and AnxA1-deficient animals suggested a potential role for AnxA1 in regulating ALX/FPRL-1 expression under pathophysiological conditions. Together, these results support a role of endogenous AnxA1 in the protective and reparative properties of the intestinal mucosal epithelium.
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