Manipulation of Distinct NFκB Proteins Alters Interleukin-1β-induced Human Rheumatoid Synovial Fibroblast Prostaglandin E2 Formation

0301 basic medicine 0303 health sciences Interleukin-8 Synovial Membrane NF-kappa B Transcription Factor RelA Membrane Proteins Fibroblasts In Vitro Techniques Oligonucleotides, Antisense Blotting, Northern Dinoprostone Phospholipases A Up-Regulation Arthritis, Rheumatoid Isoenzymes Phospholipases A2 03 medical and health sciences Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Humans Interleukin-1
DOI: 10.1074/jbc.271.49.31496 Publication Date: 2002-07-26T14:51:35Z
ABSTRACT
Interleukin 1β (IL-1β) up-regulates human rheumatoid synovial fibroblast (RSF) 85-kDa phospholipase A2 (PLA2) and mitogen-inducible cyclooxygenase (COX) II. Promoter regions for these genes contain a motif that closely resembles the "classic" NFκB consensus site. Immunoblot analysis identified NFκB1 (p50), RelA (p65), c-Rel in RSF. Upon IL-1β-stimulation, p65 but not p50 protein levels were reduced suggesting nuclear translocation. IL-1β-induced RSF extracts contained p65-containing complex, which bound to classical motif. An oligonucleotide decoy produced concentration-dependent decrease IL-1-stimulated PGE2 production (IC50 = ∼2 μM), indicating role of NFκB. Utilization antisense technology showed or mediated IL-1β-stimulated formation. Treated could transcribe COX II PLA2 mRNA, their respective proteins. Interestingly, stimulated IL-8 was inhibited by treatment with both supporting preferential binding c-Rel-p65 "alternative" κB Taken together, data provide first direct evidence gene induction support IL-1 activation participation distinct dimers prostanoid
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