| First Author | Jana M | Year | 2014 |
| Journal | Immunology | Volume | 141 |
| Issue | 4 | Pages | 549-63 |
| PubMed ID | 24224652 | Mgi Jnum | J:211495 |
| Mgi Id | MGI:5575585 | Doi | 10.1111/imm.12214 |
| Citation | Jana M, et al. (2014) Interleukin-12 (IL-12), but not IL-23, induces the expression of IL-7 in microglia and macrophages: implications for multiple sclerosis. Immunology 141(4):549-63 |
| abstractText | 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 beta1-deficient (IL-12Rbeta1(-/-)) and IL-12Rbeta2(-/-) mice, we demonstrate that IL-12 induces the expression of IL-7 in microglia and macrophages via both IL-12Rbeta2 and IL-12Rbeta1. These studies delineate a novel biological function of IL-12 that is absent in IL-23 and other p40 family members. |
