{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T11:16:29Z","timestamp":1758280589263},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1991,1,1]]},"abstract":"<jats:p>We have previously shown that recombinant interleukin 1 (IL-1) and recombinant tumour necrosis factor (TNF) synergistically stimulate phospholipase A2 release from mesangial cells. We now report that treatment of mesangial cells with the \u2032-agonist salbutamol, prostaglandin E2 (PGE2), cholera toxin or forskolin, which all activate adenylate cyclase, increased release of phospholipase A2 activity. Likewise, addition of a membrane-permeant cyclic AMP (cAMP) analogue or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine enhanced release of phospholipase A2 activity from mesangial cells. There was a lag period of about 8 h before a significantly enhanced secretion could be detected. Furthermore, actinomycin D or cycloheximide completely suppressed cAMP-stimulated secretion of phospholipase A2. Angiotensin II, the phorbol ester phorbol 12-myristate 13-acetate, the Ca2+ ionophore A23187 and a membrane-permeant cGMP analogue did not stimulate phospholipase A2 release from the cells. Treatment with indomethacin completely inhibited IL-1 \u2032- and TNF-stimulated PGE2 synthesis, without having any effect on phospholipase A2 secretion, thus excluding cytokine-induced PGE2 synthesis as the mediator of phospholipase A2 release. Neither IL-1 beta nor TNF induced any increase in intracellular cAMP in mesangial cells. Furthermore, incubation of the cells with 2\u2032,5\u2032-dideoxyadenosine, an inhibitor of adenylate cyclase, did not block cytokine-stimulated phospholipase A2 secretion. In addition, IL-1 beta and TNF synergistically interacted with forskolin to stimulate phospholipase A2 release from the cells. The protein kinase inhibitors H-8, staurosporine, K252a and amiloride inhibited IL-1 \u2032- and TNF-stimulated phospholipase A2 secretion. However, high concentrations that inhibit other protein kinases were needed. These observations suggest that IL-1 beta and TNF cause secretion of phospholipase A2 by a mechanism independent of cAMP. The signalling pathways used by IL-1 beta and TNF may involve a protein kinase that is probably different from protein kinase A or protein kinase C.<\/jats:p>","DOI":"10.1042\/bj2730199","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:19:43Z","timestamp":1439241583000},"page":"199-204","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Cyclic AMP mimics, but does not mediate, interleukin-1- and tumour-necrosis-factor-stimulated phospholipase A2 secretion from rat renal mesangial cells"],"prefix":"10.1042","volume":"273","author":[{"given":"J","family":"Pfeilschifter","sequence":"first","affiliation":[{"name":"Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd., R-1056.P.23, CH-4002 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Leighton","sequence":"additional","affiliation":[{"name":"Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd., R-1056.P.23, CH-4002 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Pignat","sequence":"additional","affiliation":[{"name":"Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd., R-1056.P.23, CH-4002 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"M\u00e4rki","sequence":"additional","affiliation":[{"name":"Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd., R-1056.P.23, CH-4002 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Vosbeck","sequence":"additional","affiliation":[{"name":"Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd., R-1056.P.23, CH-4002 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/273\/1\/199\/601788\/bj2730199.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/273\/1\/199\/601788\/bj2730199.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:51:52Z","timestamp":1637715112000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/273\/1\/199\/35929\/Cyclic-AMP-mimics-but-does-not-mediate-interleukin"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,1,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1991,1,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj2730199","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,1,1]]}}}