File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Chronic intermittent hypoxia induces local inflammation of the rat carotid body via functional upregulation of proinflammatory cytokine pathways

TitleChronic intermittent hypoxia induces local inflammation of the rat carotid body via functional upregulation of proinflammatory cytokine pathways
Authors
KeywordsCarotid body
Intermittent hypoxia
Oxidative stress
Proinflammatory cytokines
Sleep apnea
Issue Date2012
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00418/index.htm
Citation
Histochemistry And Cell Biology, 2012, v. 137 n. 3, p. 303-317 How to Cite?
AbstractMaladaptive changes in the carotid body (CB) induced by chronic intermittent hypoxia (IH) account for the pathogenesis of cardiovascular morbidity in patients with sleep-disordered breathing. We postulated that the proinflammatory cytokines, namely interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and cytokine receptors (IL-1r1, gp130 and TNFr1) locally expressed in the rat CB play a pathophysiological role in IH-induced CB inflammation. Results showed increased levels of oxidative stress (serum 8-isoprostane and nitrotyrosine in the CB) in rats with 7-day IH treatment resembling recurrent apneic conditions when compared with the normoxic control. Local inflammation shown by the amount of ED1-containing cells (macrophage infiltration) and the gene transcripts of NADPH oxidase subunits (gp91 phox and p22 phox) and chemokines (MCP-1, CCR2, MIP-1α, MIP-1β and ICAM-1) in the CB were significantly more in the hypoxic group than in the control. In addition, the cytokines and receptors were expressed in the lobules of chemosensitive glomus cells containing tyrosine hydroxylase and the levels of expressions were significantly increased in the hypoxic group. Exogenous cytokines elevated the intracellular calcium ([Ca 2+] i) response to acute hypoxia in the dissociated glomus cells. The effect of cytokines on the [Ca 2+] i response was significantly greater in the hypoxic than in the normoxic group. Moreover, daily treatment of IH rats with anti-inflammatory drugs (dexamethasone or ibuprofen) attenuated the levels of oxidative stress, gp91 phox expression and macrophage infiltration in the CB. Collectively, these results suggest that the upregulated expression of proinflammatory cytokine pathways could mediate the local inflammation and functional alteration of the CB under chronic IH conditions. © 2011 The Author(s).
Persistent Identifierhttp://hdl.handle.net/10722/146844
ISSN
2015 Impact Factor: 2.78
2015 SCImago Journal Rankings: 1.287
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong200811159058
HKU765509M
Research Grants Council, Hong KongHKU766110M
HKU7510/06M
Funding Information:

We thank Mr. W. B. Wong, Mr. Y. M. Lo and Ms. K. M. Leung for their technical assistance. This work was supported by research grants from the University of Hong Kong (200811159058, HKU765509M) and the Research Grants Council, Hong Kong (HKU766110M, HKU7510/06M).

References

 

DC FieldValueLanguage
dc.contributor.authorLam, SYen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorNg, KMen_HK
dc.contributor.authorLau, CFen_HK
dc.contributor.authorLiong, ECen_HK
dc.contributor.authorTipoe, GLen_HK
dc.contributor.authorFung, MLen_HK
dc.date.accessioned2012-05-23T05:42:30Z-
dc.date.available2012-05-23T05:42:30Z-
dc.date.issued2012en_HK
dc.identifier.citationHistochemistry And Cell Biology, 2012, v. 137 n. 3, p. 303-317en_HK
dc.identifier.issn0948-6143en_HK
dc.identifier.urihttp://hdl.handle.net/10722/146844-
dc.description.abstractMaladaptive changes in the carotid body (CB) induced by chronic intermittent hypoxia (IH) account for the pathogenesis of cardiovascular morbidity in patients with sleep-disordered breathing. We postulated that the proinflammatory cytokines, namely interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and cytokine receptors (IL-1r1, gp130 and TNFr1) locally expressed in the rat CB play a pathophysiological role in IH-induced CB inflammation. Results showed increased levels of oxidative stress (serum 8-isoprostane and nitrotyrosine in the CB) in rats with 7-day IH treatment resembling recurrent apneic conditions when compared with the normoxic control. Local inflammation shown by the amount of ED1-containing cells (macrophage infiltration) and the gene transcripts of NADPH oxidase subunits (gp91 phox and p22 phox) and chemokines (MCP-1, CCR2, MIP-1α, MIP-1β and ICAM-1) in the CB were significantly more in the hypoxic group than in the control. In addition, the cytokines and receptors were expressed in the lobules of chemosensitive glomus cells containing tyrosine hydroxylase and the levels of expressions were significantly increased in the hypoxic group. Exogenous cytokines elevated the intracellular calcium ([Ca 2+] i) response to acute hypoxia in the dissociated glomus cells. The effect of cytokines on the [Ca 2+] i response was significantly greater in the hypoxic than in the normoxic group. Moreover, daily treatment of IH rats with anti-inflammatory drugs (dexamethasone or ibuprofen) attenuated the levels of oxidative stress, gp91 phox expression and macrophage infiltration in the CB. Collectively, these results suggest that the upregulated expression of proinflammatory cytokine pathways could mediate the local inflammation and functional alteration of the CB under chronic IH conditions. © 2011 The Author(s).en_HK
dc.languageengen_US
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00418/index.htmen_HK
dc.relation.ispartofHistochemistry and Cell Biologyen_HK
dc.rightsThe original publication is available at www.springerlink.com-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectCarotid bodyen_HK
dc.subjectIntermittent hypoxiaen_HK
dc.subjectOxidative stressen_HK
dc.subjectProinflammatory cytokinesen_HK
dc.subjectSleep apneaen_HK
dc.titleChronic intermittent hypoxia induces local inflammation of the rat carotid body via functional upregulation of proinflammatory cytokine pathwaysen_HK
dc.typeArticleen_HK
dc.identifier.emailNg, KM: skykmng@hkucc.hku.hken_HK
dc.identifier.emailTipoe, GL: tgeorge@hkucc.hku.hken_HK
dc.identifier.emailFung, ML: fungml@hkucc.hku.hken_HK
dc.identifier.authorityNg, KM=rp01670en_HK
dc.identifier.authorityTipoe, GL=rp00371en_HK
dc.identifier.authorityFung, ML=rp00433en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1007/s00418-011-0900-5en_HK
dc.identifier.pmid22187044-
dc.identifier.pmcidPMC3278607-
dc.identifier.scopuseid_2-s2.0-84857625513en_HK
dc.identifier.hkuros199672en_US
dc.identifier.hkuros199913en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84857625513&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume137en_HK
dc.identifier.issue3en_HK
dc.identifier.spage303en_HK
dc.identifier.epage317en_HK
dc.identifier.isiWOS:000300326100004-
dc.publisher.placeGermanyen_HK
dc.identifier.scopusauthoridLam, SY=7402279518en_HK
dc.identifier.scopusauthoridLiu, Y=54782960800en_HK
dc.identifier.scopusauthoridNg, KM=25122990200en_HK
dc.identifier.scopusauthoridLau, CF=25122803900en_HK
dc.identifier.scopusauthoridLiong, EC=6602732210en_HK
dc.identifier.scopusauthoridTipoe, GL=7003550610en_HK
dc.identifier.scopusauthoridFung, ML=7101955092en_HK
dc.identifier.citeulike10164982-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats