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Article: Bacterial endotoxin activates retinal pigment epithelial cells and induces their degeneration through IL-6 and IL-8 autocrine signaling

TitleBacterial endotoxin activates retinal pigment epithelial cells and induces their degeneration through IL-6 and IL-8 autocrine signaling
Authors
KeywordsCytokine
Cytokine receptor
Inflammation
Lipopolysaccharide
Retinal degenerative diseases
Retinal pigment epithelial cells
Issue Date2009
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/molimm
Citation
Molecular Immunology, 2009, v. 46 n. 7, p. 1374-1386 How to Cite?
AbstractInflammation is a major contributing factor to many blinding disorders including uveitis, diabetic retinopathy, and age-related macular degeneration. Here we examined the response of the retinal pigment epithelium (RPE) to physiological levels of lipopolysaccharide (LPS) to understand the role of this epithelium in inflammatory retinal conditions. Expression of a group of inflammatory mediators was identified by gene array analysis and confirmed by PCR and immunocytochemistry in primary human RPE cultures and ARPE19. The effects of LPS on the expression of these cytokines and RPE survival were examined by PCR, Luminex bead, and MTT assays. RPE cells express many cytokine receptors including IL-1R, -4R, -6R, -8RA, IFNAR1, IFNGR1/2 and secrete a range of pro- and anti-inflammatory cytokines including IL-4, -6, -8, -10, -17, IFN-γ, MCP-1, and VEGF. LPS increases IL-13RA1 and IFNAR1, and decreases IL-7R receptor expression. It also increases RPE secretion of IL-4, -6, -8, -10, IFN-γ and MCP-1, and is toxic to RPE cells at LC50 = 17.7 μg/ml. LPS toxicity is mediated by IL-6 and IL-8 through an autocrine feedback loop. Silencing IL-6R and IL-8RA gene expression by siRNA blocks death by their respective ligands or LPS. These findings imply that RPE cells are acutely sensitive to inflammatory stress and that over secretion of IL-6 and IL-8 by this epithelium during inflammatory stimulus may be an underlying factor in the progression of some retinal pathologies. © 2008 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/169854
ISSN
2015 Impact Factor: 3.375
2015 SCImago Journal Rankings: 1.524
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, KWen_HK
dc.contributor.authorBarnstable, CJen_HK
dc.contributor.authorTombranTink, Jen_HK
dc.date.accessioned2012-10-25T04:57:05Z-
dc.date.available2012-10-25T04:57:05Z-
dc.date.issued2009en_HK
dc.identifier.citationMolecular Immunology, 2009, v. 46 n. 7, p. 1374-1386en_HK
dc.identifier.issn0161-5890en_HK
dc.identifier.urihttp://hdl.handle.net/10722/169854-
dc.description.abstractInflammation is a major contributing factor to many blinding disorders including uveitis, diabetic retinopathy, and age-related macular degeneration. Here we examined the response of the retinal pigment epithelium (RPE) to physiological levels of lipopolysaccharide (LPS) to understand the role of this epithelium in inflammatory retinal conditions. Expression of a group of inflammatory mediators was identified by gene array analysis and confirmed by PCR and immunocytochemistry in primary human RPE cultures and ARPE19. The effects of LPS on the expression of these cytokines and RPE survival were examined by PCR, Luminex bead, and MTT assays. RPE cells express many cytokine receptors including IL-1R, -4R, -6R, -8RA, IFNAR1, IFNGR1/2 and secrete a range of pro- and anti-inflammatory cytokines including IL-4, -6, -8, -10, -17, IFN-γ, MCP-1, and VEGF. LPS increases IL-13RA1 and IFNAR1, and decreases IL-7R receptor expression. It also increases RPE secretion of IL-4, -6, -8, -10, IFN-γ and MCP-1, and is toxic to RPE cells at LC50 = 17.7 μg/ml. LPS toxicity is mediated by IL-6 and IL-8 through an autocrine feedback loop. Silencing IL-6R and IL-8RA gene expression by siRNA blocks death by their respective ligands or LPS. These findings imply that RPE cells are acutely sensitive to inflammatory stress and that over secretion of IL-6 and IL-8 by this epithelium during inflammatory stimulus may be an underlying factor in the progression of some retinal pathologies. © 2008 Elsevier Ltd. All rights reserved.en_HK
dc.languageengen_US
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/molimmen_HK
dc.relation.ispartofMolecular Immunologyen_HK
dc.subjectCytokineen_HK
dc.subjectCytokine receptoren_HK
dc.subjectInflammationen_HK
dc.subjectLipopolysaccharideen_HK
dc.subjectRetinal degenerative diseasesen_HK
dc.subjectRetinal pigment epithelial cellsen_HK
dc.subject.meshAutocrine Communication - Drug Effects - Genetics - Physiologyen_US
dc.subject.meshBacterial Proteins - Pharmacologyen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshDisease Progressionen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshEndotoxins - Pharmacologyen_US
dc.subject.meshEpithelial Cells - Drug Effects - Metabolism - Pathologyen_US
dc.subject.meshGene Expression Profilingen_US
dc.subject.meshHumansen_US
dc.subject.meshInflammation - Chemically Induced - Genetics - Metabolismen_US
dc.subject.meshInterleukin-6 - Metabolism - Physiologyen_US
dc.subject.meshInterleukin-8 - Metabolism - Physiologyen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshOligonucleotide Array Sequence Analysisen_US
dc.subject.meshReceptors, Cytokine - Genetics - Metabolismen_US
dc.subject.meshRetinal Degeneration - Chemically Induced - Genetics - Metabolism - Pathologyen_US
dc.subject.meshRetinal Pigment Epithelium - Drug Effects - Metabolism - Pathologyen_US
dc.subject.meshTissue Distributionen_US
dc.titleBacterial endotoxin activates retinal pigment epithelial cells and induces their degeneration through IL-6 and IL-8 autocrine signalingen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, KW: kwleung1@hku.hken_HK
dc.identifier.authorityLeung, KW=rp01674en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.molimm.2008.12.001en_HK
dc.identifier.pmid19157552-
dc.identifier.scopuseid_2-s2.0-62549142650en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-62549142650&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume46en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1374en_HK
dc.identifier.epage1386en_HK
dc.identifier.isiWOS:000265321600011-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLeung, KW=13106059300en_HK
dc.identifier.scopusauthoridBarnstable, CJ=7006293072en_HK
dc.identifier.scopusauthoridTombranTink, J=7003724753en_HK

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