{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:40:03Z","timestamp":1772930403719,"version":"3.50.1"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[1999,9,1]],"date-time":"1999-09-01T00:00:00Z","timestamp":936144000000},"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":[[1999,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nitric oxide (NO) is an important endogenous regulatory molecule implicated in both proinflammatory and antiinflammatory processes in the lung. Previously, we demonstrated that in human alveolar macrophages (AM), NO decreased inflammatory cytokine production, including that of interleukin-1\u03b2, tumor necrosis factor-\u03b1 and macrophage inflammatory protein-1\u03b1. One mechanism by which NO could regulate such diverse cytokine production is through effects on the transcription factor nuclear factor-\u03baB (NF-\u03baB), which controls the expression of the genes for these inflammatory cytokines and growth factors. We therefore investigated whether NO affects NF-\u03baB activation in AM in vitro and in vivo. In vitro studies with AM showed that NF-\u03baB activation by lipopolysaccharide (LPS) is decreased by NO in a dose-dependent manner. NO prevented an LPS-mediated decrease in the NF-\u03baB inhibitory protein I\u03baB-\u03b1. In asthma, airway NO levels are increased, whereas in primary pulmonary hypertension (PPH), airway NO levels are lower than in healthy lungs. In vivo investigations were conducted with freshly isolated AM from healthy controls, asthmatic individuals, and PPH patients. Healthy individuals had airway NO levels of 8 \u00b1 2 ppb (mean \u00b1 SEM), which is associated with low NF-\u03baB activation. Asthma patients with airway NO levels &amp;gt;\u200217 ppb showed minimal NF-\u03baB activation, whereas asthmatic individuals with NO levels \u2264 17 ppb showed greater NF-\u03baB activation. PPH patients with low NO (1 \u00b1 1 ppb) had prominent NF-\u03baB activation. These in vivo studies in asthma and PPH support the in vitro observation of an inverse relationship between NO and NF-\u03baB activation. One mechanism by which NO blocks cytokine production involves I\u03baB.<\/jats:p>","DOI":"10.1165\/ajrcmb.21.3.3611","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T22:02:37Z","timestamp":1365026557000},"page":"311-316","source":"Crossref","is-referenced-by-count":92,"title":["Nitric Oxide Blocks Nuclear Factor-\u03ba B Activation in Alveolar Macrophages"],"prefix":"10.1093","volume":"21","author":[{"given":"Baisakhi","family":"Raychaudhuri","sequence":"first","affiliation":[{"name":"Departments of Pulmonary and Critical Care Medicine, Neurosciences, Cancer Biology, and Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raed","family":"Dweik","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary and Critical Care Medicine, Neurosciences, Cancer Biology, and Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary J.","family":"Connors","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary and Critical Care Medicine, Neurosciences, Cancer Biology, and Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Buhrow","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary and Critical Care Medicine, Neurosciences, Cancer Biology, and Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anagha","family":"Malur","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary and Critical Care Medicine, Neurosciences, Cancer Biology, and Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Drazba","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary and Critical Care Medicine, Neurosciences, Cancer Biology, and Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro C.","family":"Arroliga","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary and Critical Care Medicine, Neurosciences, Cancer Biology, and Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serpil C.","family":"Erzurum","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary and Critical Care Medicine, Neurosciences, Cancer Biology, and Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mani S.","family":"Kavuru","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary and Critical Care Medicine, Neurosciences, Cancer Biology, and Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Jane","family":"Thomassen","sequence":"additional","affiliation":[{"name":"Departments of Pulmonary and Critical Care Medicine, Neurosciences, Cancer Biology, and Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1999,9,1]]},"reference":[{"key":"2026030700105104100_B1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1164\/ajrccm.149.2.7508323","article-title":"The biology of nitrogen oxides in the airways.","volume":"149","author":"Gaston","year":"1994","journal-title":"Am. 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