Deficiency of iPLA(2)beta Primes Immune Cells for Proinflammation: Potential Involvement in Age-Related Mesenteric Lymph Node Lymphoma

作者：Inhoffen Johannes; Tuma Kellner Sabine; Straub Beate; Stremmel Wolfgang; Chamulitrat Walee^*

来源：Cancers, 2015, 7(4): 2427-2442.

DOI：10.3390/cancers7040901

• Kupffer cells
• lymphocytes
• immune response
• PLA2G6
• CD95/FasL
• M1 and Th1 cytokines
• mesenteric lymph node lymphoma

Proinflammation can predispose the body to autoimmunity and cancer. We have reported that iPLA(2)beta(-/-) mice are susceptible to autoimmune hepatitis and colitis. Here we determined whether cytokine release by immune cells could be affected by iPLA(2)beta 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 iPLA(2)beta(-/-) 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 iPLA(2)beta deficiency caused increased apoptosis in liver, spleen, and mesenteric lymph node (MLN). KC from mutant mice showed suppressed release of TNF alpha and IL-6, while their splenocytes secreted increased levels of IFN gamma 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 gamma and IL-17a by liver lymphocytes. Aged iPLA(2)beta(-/-) mice did not show follicular MLN lymphoma commonly seen in aged C57/BL6 mice. Thus, iPLA(2)beta deficiency renders M1 and Th1/Th17-proinflammation potentially leading to a reduction in age-related MLN lymphoma during aging.

• 出版日期2015-12