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The expression of iNOS in mammalian cells is governed predominantly by the transcription factor, NF-\u03baB, which regulates the expression of many host defense proteins. In the present study, we characterize a novel, biphasic effect of NO on NF-\u03baB activity in murine macrophages. This mechanism depends on the local concentration of NO and enables it both to up- and down-regulate the expression of host defense proteins including iNOS, cyclooxygenase-2, and IL-6. This biphasic activity of NO appears to play a pivotal role in the time course of activation of these immune cells and, by inference, in facilitating the initiation of a defense response against pathogenic stimuli and in its termination to limit tissue damage. This mechanism may explain at least in part the reported ability of NO to act in both a pro- and anti-inflammatory manner.<\/jats:p>","DOI":"10.4049\/jimmunol.166.6.3873","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:32:32Z","timestamp":1398022352000},"page":"3873-3881","source":"Crossref","is-referenced-by-count":264,"title":["Biphasic Regulation of NF-\u03baB Activity Underlies the Pro- and Anti-Inflammatory Actions of Nitric Oxide"],"prefix":"10.1093","volume":"166","author":[{"given":"L","family":"Connelly","sequence":"first","affiliation":[{"name":"Wolfson Institute for Biomedical Research, University College London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Palacios-Callender","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, University College London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Ameixa","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, University College London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Moncada","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, University College London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Hobbs","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, University College London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,3,15]]},"reference":[{"key":"2025032713595487600_R1","first-page":"1543","volume-title":"J. 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