Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Inflammatory mediators promote production of shed LRP1/CD91, which regulates cell signaling and cytokine expression by macrophages | |
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】
CC BY
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201904046804531ZK.pdf | 1797KB | download |