{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:13:14Z","timestamp":1791216794581,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2005,10,1]],"date-time":"2005-10-01T00:00:00Z","timestamp":1128124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>L-arginine is metabolized to nitric oxide (NO) by NO synthase (NOS), or to urea and L-ornithine by arginase. L-ornithine contributes to vascular remodeling in pulmonary hypertension via metabolism to polyamines and proline. Previously we found that cytokines upregulate both NOS and arginase in pulmonary arterial endothelial cells. We hypothesized that cytokine-induced arginase I and II expression depend on epidermal growth factor (EGF) receptor (EGFR) activity. Bovine pulmonary arterial endothelial cells were treated with lipopolysaccharide and tumor necrosis factor-\u03b1 (L\/T). L\/T treatment resulted in a substantial increase in urea production, and this increase in urea production was potently inhibited by both genistein and AG1478, inhibitors of EGFR. Levels of arginase I protein and arginase II mRNA were increased in response to L\/T treatment, and genistein prevented the L\/T-induced elevations in both arginase I protein and arginase II mRNA levels. L\/T treatment increased production of nitrites and inducible NOS mRNA accumulation, and genistein and AG1478 had little effect on these changes. EGF (50 ng\/ml) treatment resulted in enhanced urea production. Finally, a 170-kD protein was phosphorylated upon treatment with either EGF or L\/T. Our results indicate that arginase induction by L\/T depends in part on EGFR activity. We speculate that EGFR inhibitors may attenuate vascular remodeling without affecting NO release, and thus may represent novel therapeutic modalities for pulmonary hypertensive disorders.<\/jats:p>","DOI":"10.1165\/rcmb.2005-0039oc","type":"journal-article","created":{"date-parts":[[2005,7,1]],"date-time":"2005-07-01T20:17:07Z","timestamp":1120249027000},"page":"394-401","source":"Crossref","is-referenced-by-count":43,"title":["Cytokine-Induced Endothelial Arginase Expression Is Dependent on Epidermal Growth Factor Receptor"],"prefix":"10.1093","volume":"33","author":[{"given":"Leif D.","family":"Nelin","sequence":"first","affiliation":[{"name":"Centers for Developmental Pharmacology and Toxicology, Gene Therapy, and Cell and Vascular Biology, Columbus Children's Research Institute; Department of Pediatrics, The Ohio State University, Columbus, Ohio; and Children's Foundation Research Center at Le Bonheur Children's Medical Center, Department of Pediatrics, University of Tennessee Health Sciences Center at Memphis, Memphis, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis G.","family":"Chicoine","sequence":"additional","affiliation":[{"name":"Centers for Developmental Pharmacology and Toxicology, Gene Therapy, and Cell and Vascular Biology, Columbus Children's Research Institute; Department of Pediatrics, The Ohio State University, Columbus, Ohio; and Children's Foundation Research Center at Le Bonheur Children's Medical Center, Department of Pediatrics, University of Tennessee Health Sciences Center at Memphis, Memphis, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina M.","family":"Reber","sequence":"additional","affiliation":[{"name":"Centers for Developmental Pharmacology and Toxicology, Gene Therapy, and Cell and Vascular Biology, Columbus Children's Research Institute; Department of Pediatrics, The Ohio State University, Columbus, Ohio; and Children's Foundation Research Center at Le Bonheur Children's Medical Center, Department of Pediatrics, University of Tennessee Health Sciences Center at Memphis, Memphis, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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