Inflammatory mediators promote production of shed LRP1/CD91, which regulates cell signaling and cytokine expression by macrophages

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

关键词: LDL receptor‐;    related protein‐;    1;    LPS;    IFN‐;    γ;    ADAM;    MCP‐;    1/CCL2;    TNF‐;    α;    rheumatoid arthritis;    systemic lupus erythematosus;   

DOI  :  10.1189/jlb.0410220

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

LRP1isatype‐1transmembranereceptorthatmediatestheendocytosisofdiverseligands.LRP1β‐chainproteolysisresultsinreleaseofsLRP1thatispresentinhumanplasma.Inthisstudy,weshowthatLPSandIFN‐γinducesheddingofLRP1fromRAW264.7cellsandBMMsinvitro.ADAM17wasprincipallyresponsiblefortheincreaseinLRP1shedding.sLRP1wasalsoincreasedinvivoinmouseplasmafollowinginjectionofLPSandinplasmafromhumanpatientswithRAorSLE.sLRP1,whichwaspurifiedfromhumanplasma,andfull‐lengthLRP1,purifiedfrommouseliver,activatedcellsignalingwhenaddedtoculturesofRAW264.7cellsandBMMs.Robustactivationofp38MAPKandJNKwasobserved.TheIKK‐NF‐κBpathwaywastransientlyactivated.Proteinsthatbindtotheligand‐bindingclustersinLRP1failedtoinhibitsLRP1‐initiatedcellsignaling,howeveranantibodythattargetsthesLRP1Nterminuswaseffective.sLRP1inducedexpressionofregulatorycytokinesbyRAW264.7cells,includingTNF‐α,MCP‐1/CCL2,andIL‐10.TheseresultsdemonstratethatsLRP1isgeneratedininflammationandmayregulateinflammationbyitseffectsonmacrophagephysiology...

【 授权许可】

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