RESUMO
The complement system is important for the host defence against infection as well as for the development of inflammatory diseases. Here we show that C1q/TNF-related protein 6 (CTRP6; gene symbol C1qtnf6) expression is elevated in mouse rheumatoid arthritis (RA) models. C1qtnf6(-/-) mice are highly susceptible to induced arthritis due to enhanced complement activation, whereas C1qtnf6-transgenic mice are refractory. The Arthus reaction and the development of experimental autoimmune encephalomyelitis are also enhanced in C1qtnf6(-/-) mice and C1qtnf6(-/-) embryos are semi-lethal. We find that CTRP6 specifically suppresses the alternative pathway of the complement system by competing with factor B for C3(H2O) binding. Furthermore, treatment of arthritis-induced mice with intra-articular injection of recombinant human CTRP6 cures the arthritis. CTRP6 is expressed in human synoviocytes, and CTRP6 levels are increased in RA patients. These results indicate that CTRP6 is an endogenous complement regulator and could be used for the treatment of complement-mediated diseases.
Assuntos
Adipocinas/imunologia , Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Via Alternativa do Complemento/imunologia , Adipocinas/genética , Adulto , Animais , Artrite Experimental/genética , Artrite Experimental/patologia , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Reação de Arthus/genética , Reação de Arthus/imunologia , Reação de Arthus/metabolismo , Western Blotting , Colágeno/imunologia , Colágeno/metabolismo , Convertases de Complemento C3-C5/imunologia , Complemento C3a/imunologia , Complemento C5a/imunologia , Via Alternativa do Complemento/genética , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Feminino , Citometria de Fluxo , Humanos , Imunoprecipitação , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Membrana Sinovial/citologia , Membrana Sinovial/metabolismoRESUMO
PURPOSE: We describe a method for symmetrical vermilion reconstruction after resection of hemangiomas of the lip. PATIENTS AND METHODS: Four patients underwent vermilion reconstruction after resection of large cavernous hemangiomas of the lip. This reconstruction technique employed 3 basic components: 1 ) labial mucosal advancement flap, 2 ) orbicularis oris muscle flap, if necessary, and 3 ) free mucosal graft. RESULTS: All patients successfully underwent the planned procedures without significant complications. Symmetrical profiles of vermilion of the lip were achieved in all cases, even when an extended excision had been performed. CONCLUSIONS: We have found that the combination of labial mucosal advancement flaps, with or without muscular flaps, and free mucosal grafts provides excellent esthetic outcomes with a low complication rate. This method should be incorporated into the surgical techniques for symmetrical reconstruction after resection of hemangiomas of the lip.