Interleukin-8 is a Cyclosporin A binding protein
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Inflammatory immune reactions occur during transplant rejections and autoimmune diseases. Such reactions are mediated by cytokines, including interleukin-8 (IL-8). Cyclosporin A (CsA) exerts immunosuppressive activities1,2 by binding to immunoregulatory proteins termed cyclophilins3. The anti-inflammatory effects of CsA are still not fully understood. Searching for novel neutrophil-activating proteins, we observed that an antiserum against human recombinant Interleukin-8 (IL-8) cross-reacted with cyclophilins in Western blots. Furthermore, native IL-8 was found to specifically bind CsA, whereas biologically inactive analogs of CsA were not bound by IL-8. Putative binding sites for CsA on IL-8 could be identified on the basis of structural similarities between IL-8 and cyclophilin. However, IL-8 lacks peptidyl-prolyl-isomerase (PPlase) enzyme activity, which is regarded as a characteristic of cyclophilins4,5,6. We conclude that the specific binding of CsA to IL-8 may explain some of the anti-inflammatory effects of CsA. IL-8 may be a novel member of the cyclophilins lacking PPlase activity.
Key wordsCyclosporin A cyclophilin immunophilin Interleukin-8
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