PMID- 17367819 OWN - NLM STAT- MEDLINE DCOM- 20070625 LR - 20111117 IS - 0024-3205 (Print) IS - 0024-3205 (Linking) VI - 80 IP - 20 DP - 2007 Apr 24 TI - HLA-DRB1*04 gene polymorphisms and expressions profiles of interleukin-18 and interleukin-18 binding protein following in vitro stimulation in human peripheral blood mononuclear cells of healthy individuals and patients with rheumatoid arthritis. PG - 1887-96 AB - Rheumatoid arthritis (RA) is a chronic arthritic condition that can lead to deformities and disabilities. Interleukin-18 (IL-18) is a proinflammatory cytokine known to play a role in the acute and chronic inflammatory phases of RA. IL-18 binding protein is the natural antagonist of IL-18 protein. We aim to identify the effect of HLA-DRB1*04 gene polymorphisms on IL-18 and IL-18BP gene expressions profiles as well as the time-course profiles following in vitro stimulation with mitogens. Peripheral blood mononuclear cells from 16 RA patients and 21 healthy controls were cultured for 1, 4, 8, 12, 24, 48 and 72 h following stimulation with either LPS or PHA. mRNA expression of IL-18 and IL 18BP were determined by quantitative real-time PCR using a comparative Ct (threshold cycle) method. IL-18 levels in supernatants were measured by enzyme-linked immunosorbent assay. Basal mRNA (4.5-fold) and protein levels of IL-18 were increased and IL-18BP mRNA expression was decreased (8-fold) in RA patients when compared to controls. Similarly, increased IL-18 levels were observed in active RA patients, whereas IL-18BP expression was increased in inactive patients. There was an increase in mRNA and protein levels of IL-18 in RA patients that peaked at 4 h and 8 h respectively following LPS stimulation. A similar profile was observed for IL-18BP; however, the expression level was higher in controls than RA patients. Persistent high production of IL-18 in RA is associated with disease progression and IL-18 BP seems to inhibit this activity. FAU - Sivalingam, S P AU - Sivalingam SP AD - Department of Medicine, National University of Singapore, Republic of Singapore. ssuppiah@dso.org.sg FAU - Thumboo, J AU - Thumboo J FAU - Vasoo, S AU - Vasoo S FAU - Fong, K Y AU - Fong KY LA - eng PT - Comparative Study PT - Journal Article DEP - 20070224 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (HLA-DR Antigens) RN - 0 (HLA-DRB1 Chains) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Interleukin-18) RN - 0 (Lipopolysaccharides) RN - 0 (Phytohemagglutinins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Interleukin-18) RN - 0 (interleukin-18 binding protein) SB - IM MH - Arthritis, Rheumatoid/blood/*genetics MH - Gene Expression Profiling MH - HLA-DR Antigens/*genetics/metabolism MH - HLA-DRB1 Chains MH - Humans MH - Intercellular Signaling Peptides and Proteins/*genetics MH - Interleukin-18/*genetics MH - Leukocytes, Mononuclear/*physiology MH - Lipopolysaccharides/pharmacology MH - Phytohemagglutinins/pharmacology MH - *Polymorphism, Genetic MH - RNA, Messenger/drug effects/metabolism MH - Receptors, Interleukin-18/*genetics EDAT- 2007/03/21 09:00 MHDA- 2007/06/26 09:00 CRDT- 2007/03/21 09:00 PHST- 2006/10/20 00:00 [received] PHST- 2006/12/27 00:00 [revised] PHST- 2007/02/16 00:00 [accepted] PHST- 2007/03/21 09:00 [pubmed] PHST- 2007/06/26 09:00 [medline] PHST- 2007/03/21 09:00 [entrez] AID - S0024-3205(07)00183-X [pii] AID - 10.1016/j.lfs.2007.02.020 [doi] PST - ppublish SO - Life Sci. 2007 Apr 24;80(20):1887-96. doi: 10.1016/j.lfs.2007.02.020. Epub 2007 Feb 24.