title: Deficiency of iPLA₂β Primes Immune Cells for Proinflammation: Potential Involvement in Age-Related Mesenteric Lymph Node Lymphoma.
abstract: Proinflammation can predispose the body to autoimmunity and cancer. We have reported that iPLA₂β(-/-) mice are susceptible to autoimmune hepatitis and colitis. Here we determined whether cytokine release by immune cells could be affected by iPLA₂β 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 iPLA₂β(-/-) 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 iPLA₂β deficiency caused increased apoptosis in liver, spleen, and mesenteric lymph node (MLN). KC from mutant mice showed suppressed release of TNFα and IL-6, while their splenocytes secreted increased levels of IFNγ and IL-17a. Upon CD95/FasL activation, the mutant KC in turn showed exaggerated cytokine release, this was accompanied by an increased release of IFNγ and IL-17a by liver lymphocytes. Aged iPLA₂β(-/-) mice did not show follicular MLN lymphoma commonly seen in aged C57/BL6 mice. Thus, iPLA₂β deficiency renders M1- and Th1/Th17-proinflammation potentially leading to a reduction in age-related MLN lymphoma during aging.
authors.affiliation: Department of Internal Medicine IV, University Heidelberg Hospital, 69120 Heidelberg, Germany. Johannnes.Inhoffen@med.uni-heidelberg.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Inhoffen
authors.affiliation: Department of Internal Medicine IV, University Heidelberg Hospital, 69120 Heidelberg, Germany. Sabine.Tuma@med.uni-heidelberg.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Tuma-Kellner
authors.affiliation: Pathology Institute of Medical Faculty Heidelberg, 69120 Heidelberg, Germany. Beate.Straub@med.uni-heidelberg.de.
authors.forename: Beate
authors.initials: B
authors.lastname: Straub
authors.affiliation: Department of Internal Medicine IV, University Heidelberg Hospital, 69120 Heidelberg, Germany. Wolfgang.stremmel@med.uni-heidelberg.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.affiliation: Department of Internal Medicine IV, University Heidelberg Hospital, 69120 Heidelberg, Germany. Walee.Chamulitrat@med.uni-heidelberg.de.
authors.forename: Walee
authors.initials: W
authors.lastname: Chamulitrat
keywords: CD95/FasL; Kupffer cells; M1 and Th1 cytokines; PLA2G6; immune response; lymphocytes; mesenteric lymph node lymphoma