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Cyclophilin C-associated protein: a normal secreted glycoprotein that down-modulates endotoxin and proinflammatory responses in vivo.

Mouse cyclophilin C-associated protein (CyCAP) is a member of the scavenger-receptor cysteine-rich domain superfamily and is 69% identical to the human Mac-2 binding protein. Here, we show that CyCAP is a widely expressed secreted glycoprotein that modulates the host response to endotoxin. Gene-targeted CyCAP-deficient mice are more sensitive to the lethal effects of endotoxin. In response to endotoxin, CyCAP-deficient mice overproduced interleukin 12 and interferon-gamma systemically and tumor necrosis factor alpha locally; these are proinflammatory molecules that also promote T helper 1 responses. Furthermore, macrophages stimulated in vitro with endotoxin in serum deficient in CyCAP secreted more tumor necrosis factor alpha, supporting the proposal that CyCAP specifically down-modulates endotoxin signaling.

Pubmed ID: 10077627

Authors

  • Trahey M
  • Weissman IL

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

March 16, 1999

Associated Grants

  • Agency: NCI NIH HHS, Id: 5T32 CA09302

Mesh Terms

  • Animals
  • Endotoxins
  • Glycoproteins
  • Humans
  • Immunity, Innate
  • Inflammation
  • Macrophage Activation
  • Mice
  • Mice, Knockout