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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: PLoS One; v. 10, n. 4 APR 8 2015.
• Web of Science Citations: 10

Abstract

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)

• FAPESP's process: 11/23735-0 - Mechanisms involved in the modulation of the immune response induced by high molecular weight components of Ascaris suum extract and crotoxin isolated from Crotalus durissus terrificus venom
• Grantee: Eliana Faquim de Lima Mauro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/05701-9 - Evaluation of imunnomodulation induced by crotoxin isolated from Crotalus durissus terrificus in experimental model of inflammatory bowel disease
• Grantee: Caroline de Souza Almeida
• Support Opportunities: Scholarships in Brazil - Doctorate