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Article: Mechanisms of interleukin 1β-induced human airway smooth muscle hyporesponsiveness to histamine: Involvement of p38 MAPK and NF-κB

TitleMechanisms of interleukin 1β-induced human airway smooth muscle hyporesponsiveness to histamine: Involvement of p38 MAPK and NF-κB
Authors
Issue Date2001
PublisherAmerican Thoracic Society. The Journal's web site is located at http://ajrccm.atsjournals.org
Citation
American Journal Of Respiratory And Critical Care Medicine, 2001, v. 163 n. 4, p. 1010-1017 How to Cite?
AbstractWe have investigated the effect of IL-1β on histamine H 1-receptor (H 1R)-mediated inositol phosphate (IP) accumulation in human airway smooth muscle cells (HASMC) and on histamine-induced contraction of human bronchial rings. Stimulation of HASMC for 24 h with IL-1β resulted in significant loss of histamine-induced IP formation, which was associated with a reduction of histamine-induced contraction of IL-1β-treated human bronchial rings. An inhibitor of NF-κB activation, pyrrolidine dithiocarbamate, and a p38 MAPK inhibitor, blocked the IL-1β-induced H 1R desensitization, whereas anisomycin, an SAPK/JNK and p38 MAPK activator, mimicked the effect of IL-1β. IL-1β has been demonstrated to induce cox-2 expression and PGE 2 synthesis. In our study, indomethacin a cox antagonist, completely inhibited the effect of IL-1β on H 1R, whereas exogenously added PGE 2 was able to desensitize H 1R. Furthermore, H-89, a selective PKA inhibitor, antagonized the effect of IL-1β. Here, we have demonstrated that IL-1β desensitizes H 1R, which involves the activation of p38 MAPK and NF-κB, leading to the expression of cox-2 and the synthesis of PGE 2. PGE 2 increases intracellular cAMP resulting in PKA activation, which phosphorylates and functionally uncouples H 1R. Our results suggest that IL-1β protects airway smooth muscle against histamine-induced contractile responses and that bronchial hyperreactivity to histamine is not associated with proinflammatory cytokine-induced enhancement in H 1R signaling.
Persistent Identifierhttp://hdl.handle.net/10722/162457
ISSN
2015 Impact Factor: 13.118
2015 SCImago Journal Rankings: 5.832
References

 

DC FieldValueLanguage
dc.contributor.authorPype, JLen_US
dc.contributor.authorXu, Hen_US
dc.contributor.authorSchuermans, Men_US
dc.contributor.authorDupont, LJen_US
dc.contributor.authorWuyts, Wen_US
dc.contributor.authorMak, JCWen_US
dc.contributor.authorBarnes, PJen_US
dc.contributor.authorDemedts, MGen_US
dc.contributor.authorVerleden, GMen_US
dc.date.accessioned2012-09-05T05:20:06Z-
dc.date.available2012-09-05T05:20:06Z-
dc.date.issued2001en_US
dc.identifier.citationAmerican Journal Of Respiratory And Critical Care Medicine, 2001, v. 163 n. 4, p. 1010-1017en_US
dc.identifier.issn1073-449Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/162457-
dc.description.abstractWe have investigated the effect of IL-1β on histamine H 1-receptor (H 1R)-mediated inositol phosphate (IP) accumulation in human airway smooth muscle cells (HASMC) and on histamine-induced contraction of human bronchial rings. Stimulation of HASMC for 24 h with IL-1β resulted in significant loss of histamine-induced IP formation, which was associated with a reduction of histamine-induced contraction of IL-1β-treated human bronchial rings. An inhibitor of NF-κB activation, pyrrolidine dithiocarbamate, and a p38 MAPK inhibitor, blocked the IL-1β-induced H 1R desensitization, whereas anisomycin, an SAPK/JNK and p38 MAPK activator, mimicked the effect of IL-1β. IL-1β has been demonstrated to induce cox-2 expression and PGE 2 synthesis. In our study, indomethacin a cox antagonist, completely inhibited the effect of IL-1β on H 1R, whereas exogenously added PGE 2 was able to desensitize H 1R. Furthermore, H-89, a selective PKA inhibitor, antagonized the effect of IL-1β. Here, we have demonstrated that IL-1β desensitizes H 1R, which involves the activation of p38 MAPK and NF-κB, leading to the expression of cox-2 and the synthesis of PGE 2. PGE 2 increases intracellular cAMP resulting in PKA activation, which phosphorylates and functionally uncouples H 1R. Our results suggest that IL-1β protects airway smooth muscle against histamine-induced contractile responses and that bronchial hyperreactivity to histamine is not associated with proinflammatory cytokine-induced enhancement in H 1R signaling.en_US
dc.languageengen_US
dc.publisherAmerican Thoracic Society. The Journal's web site is located at http://ajrccm.atsjournals.orgen_US
dc.relation.ispartofAmerican Journal of Respiratory and Critical Care Medicineen_US
dc.titleMechanisms of interleukin 1β-induced human airway smooth muscle hyporesponsiveness to histamine: Involvement of p38 MAPK and NF-κBen_US
dc.typeArticleen_US
dc.identifier.emailMak, JCW:judymak@hku.hken_US
dc.identifier.authorityMak, JCW=rp00352en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.scopuseid_2-s2.0-0034744729en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034744729&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume163en_US
dc.identifier.issue4en_US
dc.identifier.spage1010en_US
dc.identifier.epage1017en_US
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridPype, JL=6602509935en_US
dc.identifier.scopusauthoridXu, H=8532345400en_US
dc.identifier.scopusauthoridSchuermans, M=12759695500en_US
dc.identifier.scopusauthoridDupont, LJ=7102011073en_US
dc.identifier.scopusauthoridWuyts, W=7003577710en_US
dc.identifier.scopusauthoridMak, JCW=7103323094en_US
dc.identifier.scopusauthoridBarnes, PJ=36064679400en_US
dc.identifier.scopusauthoridDemedts, MG=7103151782en_US
dc.identifier.scopusauthoridVerleden, GM=7006513432en_US

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