{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:06:58Z","timestamp":1790521618371,"version":"4.1.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2007,12,1]],"date-time":"2007-12-01T00:00:00Z","timestamp":1196467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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-\u03b1 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-\u03b1 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.<\/jats:p>","DOI":"10.4049\/jimmunol.179.12.8533","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:25:48Z","timestamp":1397849148000},"page":"8533-8543","source":"Crossref","is-referenced-by-count":117,"title":["The Required Role of Endogenously Produced Lipoxin A4 and Annexin-1 for the Production of IL-10 and Inflammatory Hyporesponsiveness in Mice"],"prefix":"10.1093","volume":"179","author":[{"given":"Danielle G","family":"Souza","sequence":"first","affiliation":[{"name":"Departamento de Bioqui\u0301mica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]},{"name":"Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio T","family":"Fagundes","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]},{"name":"Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio A","family":"Amaral","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]},{"name":"Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Cisalpino","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]},{"name":"Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirla\u0302ndia P","family":"Sousa","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ange\u0301lica T","family":"Vieira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Pinho","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]},{"name":"Departamento de Morfologia, Instituto de Cie\u0302ncias Biolo\u0301gicas, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques R","family":"Nicoli","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda Q","family":"Vieira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda M","family":"Fierro","sequence":"additional","affiliation":[{"name":"Departamento de Farmacologia, Instituto de Biologia, Universidade do Estado do Rio de Janeiro , Rio de Janeiro ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro M","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,12,15]]},"reference":[{"key":"2026012809294723800_R1","first-page":"1343","volume-title":"Microbes Infect.","year":"2000"},{"key":"2026012809294723800_R2","first-page":"868","volume-title":"Nature","year":"2002"},{"key":"2026012809294723800_R3","first-page":"879","volume-title":"Nature","year":"2002"},{"key":"2026012809294723800_R4","first-page":"201","volume-title":"Trends Pharmacol. 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