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Article: Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis: Pathogenesis and therapeutic implications

TitleRole of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis: Pathogenesis and therapeutic implications
Authors
KeywordsCD14 antigen
Lipopolysaccharide
Necrotizing enterocolitis
Pathogenesis
Therapy
Toll-like receptor 4
Issue Date2009
PublisherBaishideng Publishing Group. The Journal's web site is located at http://www.wjgnet.com/1007-9327/index.htm
Citation
World Journal Of Gastroenterology, 2009, v. 15 n. 38, p. 4745-4752 How to Cite?
AbstractAIM: To establish the roles of lipopolysaccharide (LPS)/CD14/toll-like receptor 4 (TLR4)-mediated inflammation in a rat model of human necrotizing enterocolitis (NEC). METHODS: Six pairs of intestinal samples from human NEC were collected before and after recovery for histological and molecular analysis of inflammatory cytokines and signaling components. In the rat NEC model, we isolated 10-cm jejunum segments and divided them into six groups (n = 6) for sham operation, treatment with LPS, bowel distension, combined bowel distension and LPS stimulation, and two therapeutic groups. The potential efficacy of a recombinant CD18 peptide and a monoclonal CD14 antibody was evaluated in the latter two groups. The serum and tissue levels of several inflammatory mediators were quantified by real-time polymerase chain reaction, ELISA and immunoblotting. RESULTS: Human acute phase NEC tissues displayed significant increases (P < 0.05) in levels of TLR4, CD14, myeloid differentiation protein (MD)-2, tumor necrosis factor (TNF)-α and nuclear factor-κB when compared to those after recovery. The histological and inflammatory picture of human NEC was reproduced in rats that were treated with combined bowel distension and LPS, but not in the sham-operated and other control rats. Serum levels of interleukin-6 and TNF-α were also elevated. The NEC pathology was attenuated by treating the NEC rats with a monoclonal CD14 antibody or an LPS-neutralizing peptide. CONCLUSION: LPS and distension are required to produce the histological and inflammatory features of NEC. A potential treatment option is blocking LPS activation and leukocyte infiltration. © 2009 The WJG Press and Baishideng. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/84176
ISSN
2015 Impact Factor: 2.787
2015 SCImago Journal Rankings: 1.076
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
The Research Grants Council of Hong Kong
Funding Information:

Supported by The Research Grants Council of Hong Kong to Luk JM

References

 

DC FieldValueLanguage
dc.contributor.authorChan, KLen_HK
dc.contributor.authorWong, KFen_HK
dc.contributor.authorLuk, JMen_HK
dc.date.accessioned2010-09-06T08:49:51Z-
dc.date.available2010-09-06T08:49:51Z-
dc.date.issued2009en_HK
dc.identifier.citationWorld Journal Of Gastroenterology, 2009, v. 15 n. 38, p. 4745-4752en_HK
dc.identifier.issn1007-9327en_HK
dc.identifier.urihttp://hdl.handle.net/10722/84176-
dc.description.abstractAIM: To establish the roles of lipopolysaccharide (LPS)/CD14/toll-like receptor 4 (TLR4)-mediated inflammation in a rat model of human necrotizing enterocolitis (NEC). METHODS: Six pairs of intestinal samples from human NEC were collected before and after recovery for histological and molecular analysis of inflammatory cytokines and signaling components. In the rat NEC model, we isolated 10-cm jejunum segments and divided them into six groups (n = 6) for sham operation, treatment with LPS, bowel distension, combined bowel distension and LPS stimulation, and two therapeutic groups. The potential efficacy of a recombinant CD18 peptide and a monoclonal CD14 antibody was evaluated in the latter two groups. The serum and tissue levels of several inflammatory mediators were quantified by real-time polymerase chain reaction, ELISA and immunoblotting. RESULTS: Human acute phase NEC tissues displayed significant increases (P < 0.05) in levels of TLR4, CD14, myeloid differentiation protein (MD)-2, tumor necrosis factor (TNF)-α and nuclear factor-κB when compared to those after recovery. The histological and inflammatory picture of human NEC was reproduced in rats that were treated with combined bowel distension and LPS, but not in the sham-operated and other control rats. Serum levels of interleukin-6 and TNF-α were also elevated. The NEC pathology was attenuated by treating the NEC rats with a monoclonal CD14 antibody or an LPS-neutralizing peptide. CONCLUSION: LPS and distension are required to produce the histological and inflammatory features of NEC. A potential treatment option is blocking LPS activation and leukocyte infiltration. © 2009 The WJG Press and Baishideng. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherBaishideng Publishing Group. The Journal's web site is located at http://www.wjgnet.com/1007-9327/index.htmen_HK
dc.relation.ispartofWorld Journal of Gastroenterologyen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectCD14 antigenen_HK
dc.subjectLipopolysaccharideen_HK
dc.subjectNecrotizing enterocolitisen_HK
dc.subjectPathogenesisen_HK
dc.subjectTherapyen_HK
dc.subjectToll-like receptor 4en_HK
dc.subject.meshAntigens, CD14 - metabolism-
dc.subject.meshEnterocolitis, Necrotizing - immunology - metabolism - physiopathology-
dc.subject.meshLipopolysaccharides - metabolism-
dc.subject.meshToll-Like Receptor 4 - metabolism-
dc.subject.meshTumor Necrosis Factor-alpha - blood-
dc.titleRole of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis: Pathogenesis and therapeutic implicationsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1007-9327&volume=15&issue=38&spage=4745&epage=4752&date=2009&atitle=Role+of+LPS/CD14/TLR4-mediated+inflammation+in+necrotizing+enterocolitis:+pathogenesis+and+therapeutic+implicationsen_HK
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_HK
dc.identifier.authorityLuk, JM=rp00349en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3748/wjg.15.4745en_HK
dc.identifier.pmid19824106-
dc.identifier.pmcidPMC2761550-
dc.identifier.scopuseid_2-s2.0-72249112519en_HK
dc.identifier.hkuros168585en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-72249112519&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume15en_HK
dc.identifier.issue38en_HK
dc.identifier.spage4745en_HK
dc.identifier.epage4752en_HK
dc.identifier.isiWOS:000270841600003-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChan, KL=37004089600en_HK
dc.identifier.scopusauthoridWong, KF=37096577900en_HK
dc.identifier.scopusauthoridLuk, JM=7006777791en_HK

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