{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T17:37:42Z","timestamp":1770485862224,"version":"3.49.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"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":[[2005,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Activation of the stress response attenuates proinflammatory responses by suppressing cytokine-stimulated activation of the NF-\u03baB signaling pathway. In this study, we show that the activation of the cellular stress response, either by heat shock treatment or after exposure to sodium arsenite, leads to a transient inhibition of I\u03baB\u03b1 phosphorylation. Inhibition of I\u03baB\u03b1 phosphorylation after stress was associated with the detergent insolubilization of the upstream kinases, I\u03baB kinase \u03b1 (IKK\u03b1) and I\u03baB kinase \u03b2, components involved in I\u03baB\u03b1 phosphorylation. Pretreatment of cells with glycerol, a chemical chaperone that reduces the extent of stress-induced protein denaturation, reduced the stress-dependent detergent insolubility of the IKK complex and restored the cytokine-stimulated phosphorylation of I\u03baB. The stress-dependent insolubility of the IKK complex appeared reversible; as the cells recovered from the heat shock treatment, the IKK complex reappeared within the soluble fraction of cells and was again capable of mediating the phosphorylation of I\u03baB\u03b1 in response to added cytokines. Treatment of cells with geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) function, also resulted in IKK detergent insolubility and proteasome-mediated degradation of the IKK complex. Furthermore, while IKK\u03b1 coprecipitated with Hsp90 in control cells, coprecipitation of the two proteins was greatly reduced in those cells early after stress or following exposure to geldanamycin. Stress-induced transient insolubilization of the I\u03baB kinase complex following its dissociation from Hsp90 represents a novel mechanism by which the activation of the stress response inhibits the NF-\u03baB signaling pathway in response to proinflammatory stimuli.<\/jats:p>","DOI":"10.4049\/jimmunol.174.1.384","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:56:36Z","timestamp":1398027396000},"page":"384-394","source":"Crossref","is-referenced-by-count":52,"title":["Stress-Induced Inhibition of the NF-\u03baB Signaling Pathway Results from the Insolubilization of the I\u03baB Kinase Complex following Its Dissociation from Heat Shock Protein 90"],"prefix":"10.1093","volume":"174","author":[{"given":"Jean-Francois","family":"Pittet","sequence":"first","affiliation":[{"name":"Laboratory of Surgical Research, Departments of Anesthesia and Surgery, University of California , San Francisco, CA 94110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyon","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Surgical Research, Departments of Anesthesia and Surgery, University of California , San Francisco, CA 94110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Pespeni","sequence":"additional","affiliation":[{"name":"Laboratory of Surgical Research, Departments of Anesthesia and Surgery, University of California , San Francisco, CA 94110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison","family":"O\u2019Mahony","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Virology and Immunology , San Francisco, CA 94158"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremie","family":"Roux","sequence":"additional","affiliation":[{"name":"Laboratory of Surgical Research, Departments of Anesthesia and Surgery, University of California , San Francisco, CA 94110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J","family":"Welch","sequence":"additional","affiliation":[{"name":"Laboratory of Surgical Research, Departments of Anesthesia and Surgery, University of California , San Francisco, CA 94110"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,1,1]]},"reference":[{"key":"2026020212222808200_R1","first-page":"3","volume-title":"J. 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