Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Alpha‐1‐antitrypsin inhibits nitric oxide production | |
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】
CC BY
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