{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:13:35Z","timestamp":1791270815471,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[1998,9,1]],"date-time":"1998-09-01T00:00:00Z","timestamp":904608000000},"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":[[1998,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cytokine gene expression in T lymphocytes is a strictly regulated process, involving both stimulatory and inhibitory signals. \u03b2-Adrenoceptor (\u03b2AR) agonists are widely used in the treatment of asthma and are able to induce an inhibitory signal on immunological responses after binding to their specific receptors. In this study, the characterization of \u03b2AR subtype(s) (\u03b21, \u03b22, and \u03b23) involved in the regulation of interleukin (IL)-3, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon-\u03b3 (IFN-\u03b3) mRNA accumulation was studied by using various \u03b2AR agonists and antagonists. Concanavalin A (Con A)-induced IFN-\u03b3, GM-CSF, and IL-3 mRNAs are dose-dependently inhibited by the nonselective \u03b2AR agonist isoproterenol and by the selective \u03b22AR agonist fenoterol. IL-4 mRNA accumulation was not susceptible to \u03b2AR stimulation. The observed inhibition on IFN-\u03b3, GM-CSF, and IL-3 mRNA was blocked by the selective \u03b22AR antagonist ICI 118,551 (10\u22126 M) and by timolol (10\u22126 M), a nonselective antagonist. The selective \u03b21AR antagonist atenolol (0.3 \u00d7 10\u22126 M) did not have any effect. Secretion of GM-CSF protein in the presence of increasing concentrations of isoproterenol followed a similar pattern as observed for GM-CSF mRNA. In addition, the \u03b2AR-mediated inhibition of IFN-\u03b3, GM-CSF, and IL-3 mRNA accumulation and GM-CSF protein secretion were related to the accumulation of intracellular cyclic adenosine monophosphate (cAMP) levels. Although \u03b23AR mRNA was detectable in Con A-activated T lymphocytes, we could not demonstrate a functional activity in the regulation of cytokine expression: the \u03b23AR agonist BRL 37344 had no effect on the accumulation of the studied cytokine mRNAs, and did not significantly affect cellular cAMP levels. These data demonstrate that \u03b2-agonist-induced inhibition of IFN-\u03b3, GM-CSF, and IL-3 mRNA accumulation is solely mediated by \u03b22-adrenoceptors.<\/jats:p>","DOI":"10.1165\/ajrcmb.19.3.2765","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T22:19:27Z","timestamp":1365027567000},"page":"400-407","source":"Crossref","is-referenced-by-count":91,"title":["\u03b2-Adrenoceptor-mediated Inhibition of IFN-\u03b3, IL-3, and GM-CSF mRNA Accumulation in Activated Human T Lymphocytes Is Solely Mediated by the \u03b22-Adrenoceptor Subtype"],"prefix":"10.1093","volume":"19","author":[{"given":"Peter","family":"Borger","sequence":"first","affiliation":[{"name":"Divisions of Allergology, Pulmonology, Molecular Pharmacology, and Hematology, Department of Internal Medicine and University Centre for Pharmacy, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yke","family":"Hoekstra","sequence":"additional","affiliation":[{"name":"Divisions of Allergology, Pulmonology, Molecular Pharmacology, and Hematology, Department of Internal Medicine and University Centre for Pharmacy, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariet T.","family":"Esselink","sequence":"additional","affiliation":[{"name":"Divisions of Allergology, Pulmonology, Molecular Pharmacology, and Hematology, Department of Internal Medicine and University Centre for Pharmacy, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirkje S.","family":"Postma","sequence":"additional","affiliation":[{"name":"Divisions of Allergology, Pulmonology, Molecular Pharmacology, and Hematology, Department of Internal Medicine and University Centre for Pharmacy, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Zaagsma","sequence":"additional","affiliation":[{"name":"Divisions of Allergology, Pulmonology, Molecular Pharmacology, and Hematology, Department of Internal Medicine and University Centre for Pharmacy, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edo","family":"Vellenga","sequence":"additional","affiliation":[{"name":"Divisions of Allergology, Pulmonology, Molecular Pharmacology, and Hematology, Department of Internal Medicine and University Centre for Pharmacy, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk F.","family":"Kauffman","sequence":"additional","affiliation":[{"name":"Divisions of Allergology, Pulmonology, Molecular Pharmacology, and Hematology, Department of Internal Medicine and University Centre for Pharmacy, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1998,9,1]]},"reference":[{"key":"2026030700165633000_B1","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.4049\/jimmunol.152.6.3024","article-title":"Endogenous norepinephrine regulates tumor necrosis factor-\u03b1 production from macrophages in vitro.","volume":"152","author":"Spengler","year":"1994","journal-title":"J. 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Immunol."},{"key":"2026030700165633000_B5","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1182\/blood.V87.2.691.bloodjournal872691","article-title":"Interleukin-4 gene expression in activated human T lymphocytes is regulated by the cyclic adenosine monophosphate-dependent signaling pathway.","volume":"87","author":"Borger","year":"1996","journal-title":"Blood"},{"key":"2026030700165633000_B6","first-page":"108","article-title":"Activation of the cAMP dependent signaling pathway downregulates the expression of interleukin-3 and granulocyte\/macrophage colony-stimulating factor in activated human T-lymphocytes.","volume":"24","author":"Borger","year":"1996","journal-title":"Exp. 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