Alpha‐1‐antitrypsin inhibits nitric oxide production

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: α;    ‐;    1‐;    proteinase inhibitor;    iNOS;    NF‐;    κ;    B;    MAPK;   

DOI  :  10.1189/jlb.0212071

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

NOisanendogenouslyproducedgasthatregulatesinflammation,vasculartone,neurotransmission,andimmunity.NOproductioncanbeincreasedbyexposingcellstoseveralendogenousandexogenousproinflammatorymediators,includingIFN‐γ,TNF‐α,IL‐1β,andLPS.AsAAThasbeenshowntoinhibitcellactivationandsuppresscytokineproductionassociatedwithproinflammatorystimulation,weexaminedAATforNO‐suppressivefunction.InRAW264.7murinemacrophagiccells,physiologicalAATconcentrationssignificantlyinhibitedcombinedLPS‐andIFN‐γ‐inducedNOsynthesis,andNOsynthesisinhibitionwasassociatedwithdecreasedexpressionofiNOS,suppressedNF‐κBactivation,andreducedtranslocationofextracellularAATintotheinteriorofRAW264.7cells.CE‐2072,asyntheticinhibitorofserineproteases,alsosuppressedNOproduction,iNOSexpression,andNF‐κBactivation.However,AATdidnotalteractivationofintracellularMAPKs.InsubjectswithgeneticAATdeficiency,exhaledNOwasincreasedsignificantlycomparedwithexhaledNOinhealthycontrols.TheseinvitroandinvivostudiessuggestthatAATisanendogenousinhibitorofNOproduction.AdministeringAATorAAT‐likemoleculesmayhaveuseasatreatmentfordiseasesassociatedwithexcessiveNOproduction...

【 授权许可】

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