The metalloprotease-directed shedding of BP 180 (collagen XVII) from human keratinocytes in culture is unaffected by ceramide and cell-matrix interaction.
The constitutive shedding of BP180 (collagen XVII) from human keratinocytes in culture was totally prevented by batimastat (5 microM), a wide spectrum matrix metalloprotease (MMP) inhibitor. However, keratinocytes did not express active MMP and generation of active Gelatinase A (MMP-2) and Gelatinase B (MMP-9) at the cell plasma membrane by increasing the ceramide content of keratinocytes did not influence BP180 processing to a 120 kDa species. A disintegrin and metalloprotease (ADAM) is probably involved in such a shedding event since release of 120 kDa polypeptide was inhibited by Decanoyl-Arg-Val-Lys-Arg CH2Cl (30 microM), a specific furin convertase inhibitor; culturing cells on to several matrix substrata i.e. type I collagen, type IV collagen, laminin-1 or laminin-5 had no effect on BP180 processing. Overall our data indicated that the metalloprotease-mediated shedding of BP180 from keratinocytes in culture is insensitive either to agents which activate MAP kinase pathway (ceramide) or to cell-matrix interactions.
Labrousse
Anne-Laure
AL
Department of dermatology, CNRS FRE 2260, IFR 53 Biomolecules, Faculty of Medicine, 51, rue Cognacq-Jay, 51095 Reims Cedex, France.
Buisson-Legendre
Nathalie
N
Hornebeck
William
W
Bernard
Philippe
P
D000328:Adult; D000368:Aged; D001324:Autoantigens; D002352:Carrier Proteins; D002450:Cell Communication; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D006801:Humans; D015603:Keratinocytes / Q000276:immunology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008666:Metalloendopeptidases / Q000502:physiology*; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D002518:Ceramides; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010649:Phenylalanine; D013876:Thiophenes; D000097805:Collagen Type XVII; C486268:DST protein, human; C080985:batimastat