The Required Role of Endogenously Produced Lipoxin A4 and Annexin-1 for the Production of IL-10 and Inflammatory Hyporesponsiveness in Mice
Open Access
- 15 December 2007
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 179 (12), 8533-8543
- https://doi.org/10.4049/jimmunol.179.12.8533
Abstract
The appropriate development of an inflammatory response is central for the ability of a host to deal with any infectious insult. However, excessive, misplaced, or uncontrolled inflammation may lead to acute or chronic diseases. The microbiota plays an important role in the control of inflammatory responsiveness. In this study, we investigated the role of lipoxin A4 and annexin-1 for the IL-10-dependent inflammatory hyporesponsiveness observed in germfree mice. Administration of a 15-epi-lipoxin A4 analog or an annexin-1-derived peptide to conventional mice prevented tissue injury, TNF-α production, and lethality after intestinal ischemia/reperfusion. This was associated with enhanced IL-10 production. Lipoxin A4 and annexin-1 failed to prevent reperfusion injury in IL-10-deficient mice. In germfree mice, there was enhanced expression of both lipoxin A4 and annexin-1. Blockade of lipoxin A4 synthesis with a 5-lipoxygenase inhibitor or Abs against annexin-1 partially prevented IL-10 production and this was accompanied by partial reversion of inflammatory hyporesponsiveness in germfree mice. Administration of BOC-1, an antagonist of ALX receptors (at which both lipoxin A4 and annexin-1 act), or simultaneous administration of 5-lipoxygenase inhibitor and anti-annexin-1 Abs, was associated with tissue injury, TNF-α production, and lethality similar to that found in conventional mice. Thus, our data demonstrate that inflammatory responsiveness is tightly controlled by the presence of the microbiota and that the innate capacity of germfree mice to produce IL-10 is secondary to their endogenous greater ability to produce lipoxin A4 and annexin-1.Keywords
This publication has 59 references indexed in Scilit:
- Regulation of 5-lipoxygenase enzyme activityBiochemical and Biophysical Research Communications, 2005
- Cysteinyl leukotriene receptor antagonist regulates vascular permeability by reducing vascular endothelial growth factor expressionJournal of Allergy and Clinical Immunology, 2004
- Aberrant inflammation and resistance to glucocorticoids in Annexin 1−/−MouseThe FASEB Journal, 2002
- Inflammation in atherosclerosisNature, 2002
- 15-Epi-16-(Para-Fluorophenoxy)-Lipoxin A4-Methyl Ester, a Synthetic Analogue of 15-epi-Lipoxin A4, Is Protective in Experimental Ischemic Acute Renal FailureJournal of the American Society of Nephrology, 2002
- Aspirin‐triggered lipoxin A 4 and lipoxin A 4 up‐regulate transcriptional corepressor NAB1 in human neutrophilsThe FASEB Journal, 2001
- Molecular Cloning of TA16, a Transcriptional Repressor That May Mediate Glucocorticoid-Induced Growth Arrest of Leiomyosarcoma CellsMolecular Endocrinology, 1997
- Lipoxin A4 modulates transmigration of human neutrophils across intestinal epithelial monolayers.JCI Insight, 1993
- Regulation of inflammation by lipocortin 1Immunology Today, 1992
- Inhibition of leukotriene B4-induced neutrophil migration by lipoxin A4: Structure-function relationshipsBiochemical and Biophysical Research Communications, 1991