Premium
Interleukin‐12 ( IL ‐12), but not IL ‐23, induces the expression of IL ‐7 in microglia and macrophages: implications for multiple sclerosis
Author(s) -
Jana Malabendu,
Mondal Susanta,
Jana Arundhati,
Pahan Kalipada
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12214
Subject(s) - microglia , interleukin 12 , immune system , microbiology and biotechnology , interleukin 23 , astrocyte , biology , immunology , lipopolysaccharide , interleukin , chemistry , cytokine , inflammation , central nervous system , in vitro , neuroscience , cytotoxic t cell , biochemistry
Summary Interleukin‐12 (IL‐12) p70 and IL‐23 are bioactive cytokines and their biological functions are becoming clear. Increased expression of IL‐7 in the central nervous system as well as in peripheral immune cells is associated with multiple sclerosis and experimental allergic encephalomyelitis. Here, we describe the induction of IL‐7 in primary mouse and human microglia, BV‐2 microglial cells, mouse peritoneal macrophages and astrocytes by IL‐12p70. Interestingly, IL‐12 strongly induced the expression of IL‐7 whereas IL‐23 and other p40 family members remained weak inducers of IL‐7 in these cell types. Consistently, IL‐12, but not IL‐23 and other p40 family members, induced IL‐7 promoter‐driven luciferase activity in microglial cells. Among various stimuli tested, IL‐12 emerged as the most potent stimulus followed by bacterial lipopolysaccharide and HIV‐1 gp120 in inducing the activation of IL‐7 promoter in microglial cells. Furthermore, increase in IL‐7 mRNA expression by over‐expression of IL‐12p35 subunit, but not p40 and IL‐23 p19 subunit, confirm that p35, but not p40 and p19, is responsible for the induction of IL‐7. Finally, by using primary microglia from IL‐12 receptor β 1‐deficient (IL‐12R β 1 −/− ) and IL‐12R β 2 −/− mice, we demonstrate that IL‐12 induces the expression of IL‐7 in microglia and macrophages via both IL‐12R β 2 and IL‐12R β 1. These studies delineate a novel biological function of IL‐12 that is absent in IL‐23 and other p40 family members.