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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2008.tde-11092008-125741
Document
Author
Full name
Cristina Maria Fernandes
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Teixeira, Catarina de Fatima Pereira (President)
Farsky, Sandra Helena Poliselli
Fortes, Zuleica Bruno
Mello, Suzana Beatriz Verissimo de
Tambourgi, Denise Vilarinho
Title in Portuguese
Estudos da inflamação e dor articulares em ratos e dos mecanismos da produção de TNF-a por macrófagos isolados, induzidos pela BaP1, uma metaloproteínase isolada do veneno da serpente Bothrops asper.
Keywords in Portuguese
Artrite
Dor
Inflamação
Macrófagos
Metaloproteinase
Abstract in Portuguese
As metaloproteinases são abundantes em venenos de serpentes. Estas enzimas são homólogas às de mamíferos, encontradas em níveis elevados em inflamações articulares. Neste estudo avaliou-se a capacidade da BaP1, induzir: i) a inflamação e incapacitação articulares e a participação do TNF-a e PGE2 nesses efeitos e ii) a ativação de macrófagos em cultura e a natureza de sua interação com estas células. A BaP1 induziu aumento da permeabilidade vascular, liberação de TNF-a, MMP-9 e PGE2 e acúmulo de leucócitos na cavidade articular e tecido sinovial. Ainda, induziu dor articular. O pré-tratamento dos animais com indometacina ou anti-TNF-a reduziu a dor e o influxo leucocitário, induzidos pela BaP1. A BaP1 induziu a expressão de COX-2 e de TNF-a e a liberação desta citocina, em macrófagos isolados. Nestas células detectou-se a internalização da BaP1. Em conclusão, a BaP1 induz inflamação e nocicepção articulares, dependentes de TNF-a e PGE2. A COX-2 deve estar envolvida na liberação de PGE2 e os macrófagos são alvos importantes para as ações dessa metaloproteinase.
Title in English
Studies on both rat articular inflammation and pain, and mechanisms involved in production of TNF-a by isolated macrophages induced by BaP1, a metalloproteinase isolated from Bothrops asper snake venom.
Keywords in English
Arthritis
Inflammation
Macrophages
Metalloproteinase
Pain
Abstract in English
Metalloproteinases are major enzymes in snake venoms showing high grade of homology with mammal matrix metalloproteinases, present in high levels in inflamed joints. In this study we examined the ability of BaP1, to induce: i) inflammation and hypernociception in rat articular joints and participation of TNF-a and PGE2 in these effects, and ii) activation of cultured macrophages. BaP1 increased vascular permeability, induced release of TNF-a, PGE2 and pro-MMP-9 in joint cavities, and leucocyte influx into joint cavities and synovial tissues. Moreover, BaP1 induced articular hypernociception. Treatment of animals with indomethacin or antiserum anti-TNF-a significantly reduced hypernociception and leukocyte influx induced by BaP1. Incubation of macrophages with BaP1 caused expression of TNF-a and COX-2 as well as TNF-a release. In conclusion, BaP1 induces inflammation and hypernociception in articular joints. These effects are dependent on PGE2 and TNF-a. COX-2 may contribute for BaP1-induced PGE2 release and macrophages are key targets for BaP1 induced effects.
 
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Publishing Date
2008-09-22
 
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