Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease 英文参考文献.docVIP
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Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease 英文参考文献
AlteredCirculatingLevelsofMatrixMetalloproteinases
andInhibitorsAssociatedwithElevatedType2Cytokines
inLymphaticFilarialDisease
RajamanickamAnuradha1,JovvianP.George1,NathellaPavankumar1,VasanthapuramKumaraswami2,
ThomasB.Nutman3,SubashBabu1,4*
1NationalInstitutesofHealth—InternationalCenterforExcellenceinResearch,Chennai,India,2TuberculosisResearchCenter,Chennai,India,3LaboratoryofParasitic
Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 4SAIC-Frederick, Inc., NCI-
Frederick,Frederick,Maryland,UnitedStatesofAmerica
Abstract
Background: Infection with Wuchereria bancrofti can cause severe disease characterized by subcutaneous fibrosis and
extracellular matrix remodeling. Matrix metalloproteinases (MMPs) are a family of enzymes governing extracellular
remodeling by regulating cellular homeostasis, inflammation, and tissue reorganization, while tissue-inhibitors of
metalloproteinases (TIMPs) are endogenous regulators of MMPs. Homeostatic as well as inflammation-induced balance
betweenMMPsandTIMPsisconsideredcriticalinmediatingtissuepathology.
Methods:ToelucidatetheroleofMMPsandTIMPsinfilarialpathology,wecomparedtheplasmalevelsofapanelofMMPs,
TIMPs,otherpro-fibroticfactors,andcytokinesinindividualswithchronicfilarialpathologywith(CPAg+)orwithout(CP
Ag2)activeinfectiontothosewithclinicallyasymptomaticinfections(INF)andinthosewithoutinfection(endemicnormal
[EN]).Markersofpathogenesisweredelineatedbasedoncomparisonsbetweenthetwoactivelyinfectedgroups(CPAg+
comparedtoINF)andthosewithoutactiveinfection(CPAg2comparedtoEN).
ResultsandConclusion:OurdatarevealthatanincreaseincirculatinglevelsofMMPsandTIMPsischaracteristicofthe
filarial disease process per se and not of active infection; however, filarial disease with active infection is specifically
associatedwithincreasedratiosofMMP1/TIMP4andMMP8/TIMP4aswellaswithpro-fibroticcytokines(IL-5,IL-13andTGF-
b). Our data therefore sugges
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