{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:27:51Z","timestamp":1783524471323,"version":"3.55.0"},"reference-count":67,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,12,9]],"date-time":"2015-12-09T00:00:00Z","timestamp":1449619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004875","name":"DFG","doi-asserted-by":"publisher","award":["CH288\/6-2"],"award-info":[{"award-number":["CH288\/6-2"]}],"id":[{"id":"10.13039\/100004875","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Proinflammation can predispose the body to autoimmunity and cancer. We have reported that iPLA2\u03b2\u2212\/\u2212 mice are susceptible to autoimmune hepatitis and colitis. Here we determined whether cytokine release by immune cells could be affected by iPLA2\u03b2 deficiency alone or combined with CD95\/FasL-antibody treatment in vivo. We also determined whether cancer risk could be increased in aged mutant mice. Immune cells were isolated from 3-month old male WT and iPLA2\u03b2\u2212\/\u2212 mice, and some were injected with anti-CD95\/FasL antibody for 6 h. Kupffer cells (KC) or splenocytes and liver lymphocytes were stimulated in vitro by lipopolysaccharide or concanavalinA, respectively. Whole-body iPLA2\u03b2 deficiency caused increased apoptosis in liver, spleen, and mesenteric lymph node (MLN). KC from mutant mice showed suppressed release of TNF\u03b1 and IL-6, while their splenocytes secreted increased levels of IFN\u03b3 and IL-17a. Upon CD95\/FasL activation, the mutant KC in turn showed exaggerated cytokine release, this was accompanied by an increased release of IFN\u03b3 and IL-17a by liver lymphocytes. Aged iPLA2\u03b2\u2212\/\u2212 mice did not show follicular MLN lymphoma commonly seen in aged C57\/BL6 mice. Thus, iPLA2\u03b2 deficiency renders M1- and Th1\/Th17-proinflammation potentially leading to a reduction in age-related MLN lymphoma during aging.<\/jats:p>","DOI":"10.3390\/cancers7040901","type":"journal-article","created":{"date-parts":[[2015,12,9]],"date-time":"2015-12-09T15:21:41Z","timestamp":1449674501000},"page":"2427-2442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Deficiency of iPLA2\u03b2 Primes Immune Cells for Proinflammation: Potential Involvement in Age-Related Mesenteric Lymph Node Lymphoma"],"prefix":"10.3390","volume":"7","author":[{"given":"Johannes","family":"Inhoffen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine IV, University Heidelberg Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Tuma-Kellner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, University Heidelberg Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Straub","sequence":"additional","affiliation":[{"name":"Pathology Institute of Medical Faculty Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Stremmel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, University Heidelberg Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walee","family":"Chamulitrat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, University Heidelberg Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1158\/1078-0432.CCR-08-0149","article-title":"Targeting inflammatory pathways for prevention and therapy of cancer: Short-term friend, long-term foe","volume":"15","author":"Aggarwal","year":"2009","journal-title":"Clin. 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