{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:16:33Z","timestamp":1791083793735,"version":"4.1.0"},"reference-count":41,"publisher":"Portland Press Ltd.","issue":"20","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear.<\/jats:p>\n               <jats:p>Methods: Purified recombinant human inhibitor of \u03baB kinase subunit \u03b2 (IKK\u03b2) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein.<\/jats:p>\n               <jats:p>Results: We showed that hydrogen sulfide (H2S) inhibited IKK\u03b2 activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine \u03b3-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKK\u03b2 activity directly via sulfhydrating IKK\u03b2 at cysteinyl residue 179 (C179) in purified recombinant IKK\u03b2 protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKK\u03b2 inactivation. Furthermore, to demonstrate the significance of IKK\u03b2 sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKK\u03b2. In purified IKK\u03b2 protein, C179S mutation of IKK\u03b2 abolished H2S-induced IKK\u03b2 sulfhydration and the subsequent IKK\u03b2 inactivation. In human PAECs, C179S mutation of IKK\u03b2 blocked H2S-inhibited IKK\u03b2 activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKK\u03b2 abolished the inhibitory effect of H2S on IKK\u03b2 activation and pulmonary vascular inflammation and remodeling.<\/jats:p>\n               <jats:p>Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKK\u03b2 via sulfhydrating IKK\u03b2 at Cys179 to inhibit nuclear factor-\u03baB (NF-\u03baB) pathway activation and thereby control PAEC inflammation in PAH.<\/jats:p>","DOI":"10.1042\/cs20190514","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T12:43:18Z","timestamp":1570797798000},"page":"2045-2059","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Endogenous hydrogen sulfide sulfhydrates IKK\u03b2 at cysteine 179 to control pulmonary artery endothelial cell 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