Prostaglandin E2: a potent activator of hyaluronan synthase 1 in type-B-synoviocytes.
We demonstrated earlier that the gene HAS1 is inactive in resting type-B-synoviocytes but can be readily activated by a series of proinflammatory cytokines including IL-1beta. Here we show that in type-B-synoviocytes mRNA levels for the gene COX-2 increase more than 200-fold in response to IL-1beta treatment, whereas COX-1 mRNA levels remain virtually unchanged. We tested a series of eicosanoids and demonstrate that PGE(2) is a very potent activator of HAS1 in synoviocytes. While mumol concentrations of PGI(2) are required to activate HAS1, low nmol concentrations of PGE(2) are sufficient. In addition, while two thromboxane A(2) analogs moderately activated HAS1 at higher concentrations, the lipoxygenase pathway product LTB(4) was without effect. A series of COX inhibitors blocked IL-1beta induced HAS1 activation. Similarly, sodium salicylate (NaSal) also suppressed IL-1beta induced HAS1 activation. Furthermore, electrophoretic mobility shift assays and PGE(2) ELISA experiments demonstrate that NaSal completely prevents PGE(2) release but does not interfere with NF-kappaB translocation. PGE(2) is a very powerful activator of HAS1 transcription and translation. Such data indicate that the effect of IL-1beta on HAS1 is mediated by prostaglandins. Additionally, NaSal is a potent suppressor of HAS1 activation. These findings point towards HAS1 as a gene of importance in inflammation.
Stuhlmeier
Karl M
KM
Ludwig Boltzmann Institute for Rheumatology and Balneology, Kurbadstrasse 10, 1100 Vienna, Austria. karlms@excite.com
D001483:Base Sequence; D051546:Cyclooxygenase 2 / Q000235:genetics; D017931:DNA Primers; D015232:Dinoprostone / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D020536:Enzyme Activators / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D000076002:Hyaluronan Synthases; D053583:Interleukin-1beta / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
D017931:DNA Primers; D020536:Enzyme Activators; D053583:Interleukin-1beta; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D015232:Dinoprostone