Airwayepitheliumisemergingasaregulatorofinnateimmuneresponsestoa varietyofinsultsincludingcigarettesmoke.Themaingoalofthisstudywas to exploretheeffectsofcigarettesmokeextracts(CSE)inthetolllikereceptor (TLR) expressionandactivationinahumanbronchialepithelialcellline(16- HBE). CSEincreasedtheexpressionofTLR4andtheLPSbinding,theNFkB activation,thereleaseofIL-8andthechemotacticactivitytowardneutrophilsbut did notinducetheTLR2expressionandtheERK1/2activation.LPSincreasedthe expressionofTLR4andinducedbothNFkBandErk1/2activation.Thecombined exposureof16-HBEtoCSEandLPS,furtherincreasedIL-8releaseandthe chemotactic activitytowardneutrophils.Theseadditiveeffectswereassociated to ERKactivationratherthantoNFkBactivation.Furthermore,CSEdecreased the constitutiveIP-10releaseandcounteractedtheeffectofLPSininducing IP-10 release.Inconclusion,cigarettesmokecontributestotheaccumulationof neutrophils withintheairwaysofsmokersbyincreasingtheexpressionofTLR4 and bypreferentiallyorientatingTLR4activationtowardactivationofERKand IL-8 production. SupportedbyGlaxoSmithKline
Cigarette smoke increases TLR4 expression and modifies LPS mediated responses in airway epithelial cells.
E Pace;MFerraro;MR Bonsignore;
2007
Abstract
Airwayepitheliumisemergingasaregulatorofinnateimmuneresponsestoa varietyofinsultsincludingcigarettesmoke.Themaingoalofthisstudywas to exploretheeffectsofcigarettesmokeextracts(CSE)inthetolllikereceptor (TLR) expressionandactivationinahumanbronchialepithelialcellline(16- HBE). CSEincreasedtheexpressionofTLR4andtheLPSbinding,theNFkB activation,thereleaseofIL-8andthechemotacticactivitytowardneutrophilsbut did notinducetheTLR2expressionandtheERK1/2activation.LPSincreasedthe expressionofTLR4andinducedbothNFkBandErk1/2activation.Thecombined exposureof16-HBEtoCSEandLPS,furtherincreasedIL-8releaseandthe chemotactic activitytowardneutrophils.Theseadditiveeffectswereassociated to ERKactivationratherthantoNFkBactivation.Furthermore,CSEdecreased the constitutiveIP-10releaseandcounteractedtheeffectofLPSininducing IP-10 release.Inconclusion,cigarettesmokecontributestotheaccumulationof neutrophils withintheairwaysofsmokersbyincreasingtheexpressionofTLR4 and bypreferentiallyorientatingTLR4activationtowardactivationofERKand IL-8 production. SupportedbyGlaxoSmithKlineI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
