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Doctoral Thesis
DOI
10.11606/T.42.2014.tde-24092014-173712
Document
Author
Full name
Caroline de Souza Almeida
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Mauro, Eliana Faquim de Lima (President)
Ferreira, Ana Paula
Franco, Marcelo de
Rodriguez, Dunia Del Carmen
Vessoni, Sandra Coccuzzo Sampaio
Title in Portuguese
Estudo da imunomodulação induzida pela crotoxina do veneno de Crotalus durissus terrificus em modelo experimental de doença inflamatória no intestino.
Keywords in Portuguese
Crotalus durissus terrificus
Células T reguladoras e Th17
Crotoxina
Imunomodulação
Inflamação intestinal
TNBS
Abstract in Portuguese
Neste trabalho foi estudado o potencial imunorregulador da crotoxina (CTX) obtida do veneno de C. d. terrificus, em modelo experimental de colite induzida pelo TNBS em camundongos. A CTX foi capaz de diminuir a perda de peso, o score clínico e histológico, síntese de MPO e citocinas pró-inflamatórias. Menor número de neutrófilos e macrófagos com fenótipos M1 e M2 na lâmina própria foi observado nos grupos TNBS/CTX em relação ao TNBS. A CTX induziu TGF-b e IL-10, PGE2 e LXA4. A neutralização in vivo dessas citocinas ou o bloqueio da síntese desses eicosanoides indica que estas moléculas exercem papel relevante na ação moduladora da CTX no quadro inflamatório. As análises das diferentes populações celulares da lâmina própria, linfonodos e Placas de Peyer mostraram que não houve diferença nos linfócitos CD4+Tbet+ entre os grupos TNBS e TNBS/CTX. No entanto, a CTX promoveu aumento de CD4+FoxP3+ e diminuição de CD4+RORg+. Estes resultados indicam que a CTX é capaz de modular a resposta inflamatória aguda intestinal melhorando o quadro clinico observado nos animais.
Title in English
Evaluation of immunomodulation induced by crotoxin from Crotalus durissus terrificus snake venom in experimental model of inflammatory bowel disease.
Keywords in English
Crotalus durissus terrificus
Crotoxin
Immunomodulation
Inflammatory bowel disease
T regulatory and Th17 cells
TNBS
Abstract in English
In this work it was analyzed the immunomodulatory effect of crotoxin (CTX) isolated from C.d. terrificus snake venom, on the experimental model of colitis induced by TNBS in mice. The CTX was able to inhibit the weight loss, clinical and histological score, MPO synthesis and pro-inflammatory cytokines. Lower number of neutrophils and macrophage (M1 and M2) in lamina propria was observed in TNBS/CTX mice compared with the TNBS group. In contrast, the CTX induced increased TGF-b, IL-10, PGE2 and LXA4. The in vivo neutralization of these cytokines or eicosanoids synthesis indicates that these molecules exert significant role in the modulatory effect of CTX. The analyzes of distinct cell populations from lamina propria, lymph nodes and Peyers pathes showed no difference in CD4+Tbet+ between TNBS or TNBS/CTX mice. However, CTX induced an increase of CD4+FoxP3+ and decreased CD4+RORgt+. Together, these results indicate that CTX is able to modulate intestinal acute inflammatory response induced by TNBS improving the clinical status of the mice.
 
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Publishing Date
2014-10-07
 
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