Interleukin-12 upregulates the IL-18Rbeta chain in BALB/c thymocytes.
Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in innate immunity and specific Th1 immune responses. During infection, IL-18 is produced by activated macrophages and primarily induces interferon-gamma (IFN-gamma) production in synergy with IL-12 in primed T cells and natural killer (NK) cells. IL-18 exerts its function by binding to a specific receptor complex (IL-18R) consisting of two subunits, the IL-18Ralpha chain and the IL-18Rbeta chain. Two individual mechanisms for synergism between IL-12 and IL-18 have been reported. First, IL-12-induced expression of the IL-18 receptor complex was described. Second, IL-18 and IL-12 together induced expression of target genes on a transcriptional level. In this study, we show that freshly isolated thymocytes from BALB/c mice constitutively expressed mRNA for the IL-18Ralpha chain but not for the IL-18Rbeta chain. These thymocytes were unresponsive to IL-18. Treatment with a combination of concanavalinA (ConA) plus IL-12 did not affect expression of the IL-18Ralpha chain but strongly induced expression for IL-18Rbeta mRNA, rendering these thymocytes highly responsive to IL-18 treatment. Thus, the synergistic effects of IL-12 and IL-18 on BALB/c mouse thymocytes resulted from the induction and regulation of the IL-18Rbeta chain and not the IL-18Ralpha chain.
Neumann
D
D
Pharmacology OE 5320, Hannover Medical School, D-30623 Hannover, Germany.
Martin
M U
MU
D000818:Animals; D002460:Cell Line; D005260:Female; D007155:Immunologic Factors / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D053727:Interleukin-18 Receptor alpha Subunit; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics; D053724:Receptors, Interleukin-18; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
C508573:Il18r1 protein, mouse; D007155:Immunologic Factors; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D018664:Interleukin-12