Crotoxin from Crotalus durissus terrificus Is Able to Down-Modulate the Acute Intestinal Inflammation in Mice

Autor(es)

Almeida, Caroline de Souza ^[1] ; Andrade-Oliveira, Vinicius ^[2] ; Saraiva Camara, Niels Olsen ^[2] ; Jacysyn, Jacqueline F. ^[3] ; Faquim-Mauro, Eliana L. ^[1]

Afiliação do(s) autor(es)

^[1] Butantan Inst, Immunopathol Lab, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Dept Immunol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, LIM62, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 4 APR 8 2015.
• Citações Web of Science: 10

Resumo

Inflammatory bowel diseases (IBD) is the result of dysregulation of mucosal innate and adaptive immune responses. Factors such as genetic, microbial and environmental are involved in the development of these disorders. Accordingly, animal models that mimic human diseases are tools for the understanding the immunological processes of the IBD as well as to evaluate new therapeutic strategies. Crotoxin (CTX) is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the modulatory effect of CTX in a murine model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The CTX was administered intraperitoneally 18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX administration resulted in decreased weight loss, disease activity index (DAI), macroscopic tissue damage, histopathological score and myeloperoxidase (MPO) activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of TNF-alpha, IL-1 beta and IL-6 were lower in colon tissue homogenates of TNBS-mice that received the CTX when compared with untreated TNBS mice. The analysis of distinct cell populations obtained from the intestinal lamina propria showed that CTX reduced the number of group 3 innate lymphoid cells (ILC3) and Th17 population; CTX decreased IL-17 secretion but did not alter the frequency of CD4(+) Tbet(+) T cells induced by TNBS instillation in mice. In contrast, increased CD4(+) FoxP3(+) cell population as well as secretion of TGF-beta, prostaglandin E-2 (PGE(2)) and lipoxin A(4) (LXA(4)) was observed in TNBS-colitis mice treated with CTX compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to modulate the intestinal acute inflammatory response induced by TNBS, resulting in the improvement of clinical status of the mice. This effect of CTX is complex and involves the suppression of the pro-inflammatory environment elicited by intrarectal instillation of TNBS due to the induction of a local anti-inflammatory profile in mice. (AU)

• Processo FAPESP: 11/23735-0 - Mecanismos envolvidos na modulação da resposta imune induzidos por antígenos de alta massa molecular do extrato de Ascaris suum e crotoxina isolada do veneno de Crotalus durissus terrificus
• Beneficiário: Eliana Faquim de Lima Mauro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/05701-9 - Estudo da imunomodulação induzida pela crotoxina do veneno de Crotalus durissus terrificus em modelo experimental de doença inflamatória intestinal
• Beneficiário: Caroline de Souza Almeida
• Modalidade de apoio: Bolsas no Brasil - Doutorado