Cyclophilin C-associated protein: A normal secreted glycoprotein that down-modulates endotoxin and proinflammatory responsesin vivo

Abstract

Mouse cyclophilin C-associated protein (Cy-CAP) 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, CyCAPdeficient mice overproduced interleukin 12 and interferon-␥ systemically and tumor necrosis factor ␣ 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 ␣, supporting the proposal that CyCAP specifically down-modulates endotoxin signaling.

Cyclophilin C-Associated Protein and Cyclophilin C mRNA are Upregulated in Penumbral Neurons and Microglia after Focal Cerebral Ischemia

“…The release of cytotoxins might be the main cause of microglia-and neutrophil-mediated damage during and after ischemia. A gene-targeted study provided interesting results with regard to the function of CyCAP, showing more sensitivity to the lethal effects of endotoxin (Trahey and Weissman, 1999). Cyclophilin C-associated protein-deficient mice overproduced proinflammatory cytokines such as IL-12, interferon-g, and TNF-a in response to endotoxin.…”

“…Cyclophilin C-associated protein is regarded as a candidate for the natural cellular ligand for cyclophilin C because the interaction is inhibited by cyclosporin A (Friedman and Weissman, 1991). Moreover, CyCAP has a protective effect in the response to endotoxins by downmodulating the proinflammatory response in vivo (Trahey and Weissman, 1999). Therefore, CyCAP is regarded as an endogenous immunophilin ligand with a potentially potent neuroprotective antiinflammatory effect during cerebral infarction like immunosuppressant drug cyclosporin A and FK506.…”

Induction of Mac-2BP by nerve growth factor is regulated by the PI3K/Akt/NF-κB-dependent pathway in the HEK293 cell line

“…The reported evidence implicates Mac-2BP as a diagnostic and/or prognostic marker of poor outcome in several tumor types. Mac-2BP, like other members of its family, is involved in the host response to tumors and infections (10). Moreover, several reports have shown that the protein may function in cell adhesion processes.…”

β-Arrestin 2 Negatively Regulates Toll-like Receptor 4 (TLR4)-triggered Inflammatory Signaling via Targeting p38 MAPK and Interleukin 10

“…D-Galactosamine sensitizes mice to LPS treatment (12,29). In comparison, when the mice were treated with LPS alone, they survive longer as we saw in our studies (30,31). Thus, survival time of mice in this endotoxic shock model varies depending on D-galactosamine treatment.…”