{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:05:20Z","timestamp":1786133120174,"version":"build-2736575974"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,5]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract.<\/jats:title>\n                    <jats:p>\n                      Nitric oxide (NO) is emerging as a key regulator of gene expression, capable of playing either positive or negative roles. The results of this study indicate that NO exerts a dual effect on cyclooxygenase-2 (COX-2) expression in human mesangial cells (HMC). Treatment of HMC with NO synthase inhibitors attenuated interleukin-1\u03b2 (IL-1\u03b2)\/tumor necrosis factor-\u03b1 (TNF-\u03b1)-elicited COX-2 protein and mRNA expression, suggesting a positive role of endogenous NO on COX-2 induction. However, NO donors (sodium nitroprusside [SNP] and S-nitroso-\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -acetylpenicillamine [SNAP]) amplified cytokine-elicited COX-2 expression at early time points of treatment (up to 8 h for mRNA and up to 24 h for protein expression), but were inhibitory at later times. Oligonucleotide decoy experiments confirmed the importance of nuclear factor \u03baB (NF-\u03baB) activation for COX-2 induction by IL-1\u03b2\/TNF-\u03b1. Treatment with\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      <jats:sup>G<\/jats:sup>\n                      -nitro-L-arginine methyl ester (L-NAME) did not affect initial activation of NF-\u03baB by IL-1\u03b2\/TNF-\u03b1, but unveiled an inhibitory effect of NO generation on NF-\u03baB activity after 4 h. In HMC supplemented with SNP, cytokine-induced NF-\u03baB activation was potentiated at early times of induction (5 to 15 min), but inhibited at later times (1 to 4 h), suggesting a dual effect of NO donors on NF-\u03baB activation. Interestingly, I\u03baB\u03b1 protein levels followed a reciprocal pattern of expression: I\u03baB\u03b1 levels were lower at early times of induction in NO donor-supplemented cells; however, after 1 h of treatment, I\u03baB\u03b1 levels became higher than in cells treated only with cytokines. In the presence of SNP, cytokine-elicited I\u03baB\u03b1 mRNA induction was initially delayed, but was amplified at later times. These changes in I\u03baB\u03b1 expression could contribute to the dual effects of NO donors on NF-\u03baB activation and COX-2 expression in HMC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.v105943","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T06:06:24Z","timestamp":1619589984000},"page":"943-952","source":"Crossref","is-referenced-by-count":47,"title":["Dual Effect of Nitric Oxide Donors on Cyclooxygenase-2 Expression in Human Mesangial Cells"],"prefix":"10.1681","volume":"10","author":[{"given":"MANUELA","family":"D\u00cdAZ-CAZORLA","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DOLORES","family":"P\u00c9REZ-SALA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SANTIAGO","family":"LAMAS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-199905000-00004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:28:58Z","timestamp":1786130938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-199905000-00004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,5]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1999]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.v105943","relation":{},"ISSN":["1046-6673"],"issn-type":[{"value":"1046-6673","type":"print"}],"subject":[],"published":{"date-parts":[[1999,5]]}}}