Identification of cyclophilin as a proinflammatory secretory product of lipopolysaccharide-activated macrophages
Autor: | Anthony Cerami, Barbara Sherry, Annie Strupp, Nuriza Yarlett |
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Jazyk: | angličtina |
Rok vydání: | 1992 |
Předmět: |
Lipopolysaccharides
Isomerase activity Lipopolysaccharide Neutrophils Swine medicine.medical_treatment Molecular Sequence Data Cyclosporins Biology Peptide Mapping Proinflammatory cytokine chemistry.chemical_compound Mice Cyclosporin a Sequence Homology Nucleic Acid medicine polycyclic compounds Escherichia coli Animals Humans Trypsin Amino Acid Sequence Cyclophilin Cells Cultured Amino Acid Isomerases Peptidylprolyl isomerase Inflammation Multidisciplinary Macrophage Activation Peptidylprolyl Isomerase Molecular biology Culture Media Mice Inbred C57BL Molecular Weight Chemotaxis Leukocyte Cytokine Secretory protein chemistry Leukocytes Mononuclear Carrier Proteins Research Article |
Popis: | We have isolated an 18-kDa peptide (designated sp18, for 18-kDa secreted protein) from the conditioned medium of lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Purified sp18 had in vivo inflammatory activity and in vitro chemotactic activity for human peripheral blood polymorphonuclear leukocytes and monocytes. Surprisingly, N-terminal sequencing and tryptic mapping studies revealed that sp18 and cyclophilin, an intracellular protein that binds the immunosuppressive drug cyclosporin A, are highly homologous. The in vitro chemotactic activity of sp18 on monocytes was blocked by cyclosporin A but not by cyclosporin H, a structural analog of cyclosporin A that does not bind cyclophilin. Like purified porcine cyclophilin, mouse sp18 exhibited peptidyl-prolyl cis-trans isomerase activity. Medium conditioned by lipopolysaccharide-stimulated resident peritoneal exudate macrophages isolated from C57BL/6 mice contained substantially higher levels of sp18/cyclophilin than medium conditioned by nonstimulated macrophages. The observation that sp18/cyclophilin exhibits proinflammatory activity and is secreted by macrophages in response to endotoxin suggests that this protein may function as a cytokine, and invites the hypothesis that the immunosuppressive action of cyclosporin A results in part from interaction with an extracellular form of cyclophilin released as a mediator of immune and inflammatory functions. |
Databáze: | OpenAIRE |
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