Role of Mast Cells in Inflammatory Bowel Disease and Inflammation-Associated Colorectal Neoplasia in IL-10-Deficient Mice 英文参考文献.docVIP

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Role of Mast Cells in Inflammatory Bowel Disease and Inflammation-Associated Colorectal Neoplasia in IL-10-Deficient Mice 英文参考文献.doc

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Role of Mast Cells in Inflammatory Bowel Disease and Inflammation-Associated Colorectal Neoplasia in IL-10-Deficient Mice 英文参考文献

RoleofMastCellsinInflammatoryBowelDiseaseand Inflammation-AssociatedColorectalNeoplasiain IL-10-DeficientMice MaciejChichlowski1,GregS.Westwood1,SomanN.Abraham1,2,3,LauraP.Hale1,4 * 1DepartmentofPathology,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStatesofAmerica,2DepartmentofMolecularGeneticsandMicrobiology, Duke University Medical Center, Durham, North Carolina, United States of America, 3Department of Immunology, Duke University Medical Center, Durham, North Carolina,UnitedStatesofAmerica,4TheHumanVaccineInstitute,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStatesofAmerica Abstract Background: Inflammatory bowel disease (IBD) is hypothesized to result from stimulation of immune responses against residentintestinalbacteriawithinageneticallysusceptiblehost.MastcellsmayplayacriticalroleinIBDpathogenesis,since theyaretypicallylocatedjustbeneaththeintestinalmucosalbarrierandcanbeactivatedbybacterialantigens. Methodology/PrincipalFindings:Thisstudyinvestigatedeffectsofmastcellsoninflammationandassociatedneoplasiain IBD-susceptibleinterleukin(IL)-10-deficientmicewithandwithoutmastcells.IL-10-deficientmastcellsproducedmorepro- inflammatory cytokines in vitro both constitutively and when triggered, compared with wild type mast cells. However despitethisenhancedinvitroresponse,mastcell-sufficientIl102/2miceactuallyhaddecreasedcecalexpressionoftumor necrosis factor (TNF) and interferon (IFN)-c mRNA, suggesting that mast cells regulate inflammation in vivo. Mast cell deficiency predisposed Il102/2 mice to the development of spontaneous colitis and resulted in increased intestinal permeabilityinvivothatprecededthedevelopmentofcoloninflammation.However,mastcelldeficiencydidnotaffectthe severity of IBD triggered by non-steroidal anti-inflammatory agents (NSAID) exposure or helicobacter infection that also affectintestinalpermeability. Conclusions/Significance:Mastcellsthusappeartohaveaprimarilyprotectiverolewithinthecolonicmicroenvironment byenhancingth