PMID- 11559442 OWN - NLM STAT- MEDLINE DCOM- 20011204 LR - 20071115 IS - 1079-9907 (Print) IS - 1079-9907 (Linking) VI - 21 IP - 8 DP - 2001 Aug TI - Interleukin-12 upregulates the IL-18Rbeta chain in BALB/c thymocytes. PG - 635-42 AB - 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. FAU - Neumann, D AU - Neumann D AD - Pharmacology OE 5320, Hannover Medical School, D-30623 Hannover, Germany. FAU - Martin, M U AU - Martin MU LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Interferon Cytokine Res JT - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research JID - 9507088 RN - 0 (Il18r1 protein, mouse) RN - 0 (Immunologic Factors) RN - 0 (Interleukin-18) RN - 0 (Interleukin-18 Receptor alpha Subunit) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Interleukin) RN - 0 (Receptors, Interleukin-18) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - Cell Line MH - Female MH - Immunologic Factors/physiology MH - Interleukin-12/*physiology MH - Interleukin-18/genetics/*metabolism MH - Interleukin-18 Receptor alpha Subunit MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - RNA, Messenger/biosynthesis MH - Receptors, Interleukin/*biosynthesis/genetics MH - Receptors, Interleukin-18 MH - T-Lymphocytes/*immunology/*metabolism MH - Up-Regulation/genetics/*immunology EDAT- 2001/09/18 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/09/18 10:00 PHST- 2001/09/18 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/09/18 10:00 [entrez] AID - 10.1089/10799900152547902 [doi] PST - ppublish SO - J Interferon Cytokine Res. 2001 Aug;21(8):635-42. doi: 10.1089/10799900152547902.