Uromodulin, an immunosuppressive protein derived from pregnancy urine, is an inhibitor of interleukin 1.

AUTOR(ES)

Brown, K M

RESUMO

Uromodulin, an 85-kDa glycoprotein isolated from pregnancy urine, has been shown to inhibit antigen-induced proliferation of human lymphocytes in vitro. The present investigation was undertaken to determine its mechanism of action. Uromodulin was found to be a potent inhibitor of interleukin 1 (IL-1)-induced thymocyte proliferation. Uromodulin was compared to a previously described 30- to 35-kDa IL-1 inhibitor isolated from urine of febrile patients (febrile inhibitor). Uromodulin and the febrile inhibitor blocked the effects of both human IL-1 and recombinant murine IL-1, but the activity of uromodulin was greater than that of the only partially purified febrile inhibitor preparation. However, in contrast to the febrile inhibitor, uromodulin markedly enhanced interleukin 2-induced thymocyte proliferation. Antigenic analysis of the two preparations by ELISA and immunoblot analysis demonstrated that the febrile inhibitor did not cross-react with uromodulin using monoclonal or polyclonal antisera. These findings indicate that uromodulin is a potent IL-1 inhibitor that is probably distinct from the IL-1 inhibitor derived from the urine of febrile individuals. Whether this IL-1 inhibitory activity underlies its immunosuppressive activity on human lymphocytes remains to be established.

Documentos Relacionados

• GP2, the homologue to the renal cast protein uromodulin, is a major component of intraductal plugs in chronic pancreatitis.
• Prostaglandin E2 and collagenase production by fibroblasts and synovial cells is regulated by urine-derived human interleukin 1 and inhibitor(s).
• Monocyte-derived inhibitor of interleukin 1 induced by human cytomegalovirus.
• Localization of an antiviral site on the pregnancy recognition hormone, ovine trophoblast protein 1.
• Schistosomal egg granuloma-derived fibroblast-stimulating factor is apparently distinct from interleukin-1.