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In this article, we show that p53 has a novel inflammation-promoting action in the intestinal tract, because loss of p53 or the upstream activating kinase, ATM, protects against acute intestinal inflammation in murine models. Mechanistically, deficiency in p53 leads to increased survival of epithelial cells and lamina propria macrophages, higher IL-6 expression owing to enhanced glucose-dependent NF-\u03baB activation, and increased mucosal STAT3 activation. Blockade or loss of IL-6 signaling reverses the protective effects of p53 deficiency. Conversely, IL-6 treatment protects against acute colitis in a manner dependent on STAT3 signaling and induction of cytoprotective factors in epithelial cells. Together, these results indicate that p53 promotes inflammation in the intestinal tract through suppression of epithelium-protective factors, thus significantly expanding the spectrum of physiological and immunological p53 activities unrelated to cancer formation.<\/jats:p>","DOI":"10.4049\/jimmunol.1201716","type":"journal-article","created":{"date-parts":[[2013,6,15]],"date-time":"2013-06-15T04:10:33Z","timestamp":1371269433000},"page":"837-847","source":"Crossref","is-referenced-by-count":35,"title":["<i>Trp53<\/i> Deficiency Protects against Acute Intestinal Inflammation"],"prefix":"10.1093","volume":"191","author":[{"given":"Martina E","family":"Spehlmann","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolin F","family":"Manthey","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara M","family":"Dann","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine","family":"Hanson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukhman S","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linus Y","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farid K","family":"Abdelmalak","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela A","family":"Diamanti","sequence":"additional","affiliation":[{"name":"Institute of Molecular Immunology, Klinikum Rechts der Isar, Technical University of Munich , 81675 Munich,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Retzlaff","sequence":"additional","affiliation":[{"name":"Institute of Molecular Immunology, Klinikum Rechts der Isar, Technical University of Munich , 81675 Munich,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Scheller","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University of Kiel , 24098 Kiel,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Rose-John","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian-Albrechts-University of Kiel , 24098 Kiel,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian R","family":"Greten","sequence":"additional","affiliation":[{"name":"Institute of Molecular Immunology, Klinikum Rechts der Isar, Technical University of Munich , 81675 Munich,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Y J","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Center, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Eckmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"2025032405074847900_r1","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/cdd.2010.35","article-title":"p53-family proteins and their regulators: hubs and spokes in tumor suppression","volume":"17","author":"Collavin","year":"2010","journal-title":"Cell Death Differ."},{"key":"2025032405074847900_r2","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0092-8674(00)81871-1","article-title":"p53, the cellular gatekeeper for growth and division","volume":"88","author":"Levine","year":"1997","journal-title":"Cell"},{"key":"2025032405074847900_r3","doi-asserted-by":"crossref","first-page":"43604","DOI":"10.1074\/jbc.M106570200","article-title":"Analyses of p53 target genes in the human genome by bioinformatic and microarray approaches","volume":"276","author":"Wang","year":"2001","journal-title":"J. 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