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Crotoxin from Crotalus durissus terrificus is able to down-modulate the acute intestinal inflammation in mice.

Almeida Cde S, Andrade-Oliveira V, Câmara NO, Jacysyn JF, Faquim-Mauro EL - PLoS ONE (2015)

Bottom Line: Crotoxin (CTX) is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect.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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunopathology, Butantan Institute, São Paulo, São Paulo, Brazil.

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-α, IL-1β 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-β, prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) 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.

No MeSH data available.


Related in: MedlinePlus

Secretion of pro-inflammatory cytokines in colonic tissue homogenates of TNBS-mice treated or not with CTX.Production of IL-1β (A), IL-6 (B) and TNF-α (C) was measured in homogenates of colonic segments by ELISA. The results represent the mean of the cytokine secretion in individual mice/group ± SEM. * p<0.05, ** p<0.01 and *** p<0.001 (n = 4–5 animals/group).
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pone.0121427.g002: Secretion of pro-inflammatory cytokines in colonic tissue homogenates of TNBS-mice treated or not with CTX.Production of IL-1β (A), IL-6 (B) and TNF-α (C) was measured in homogenates of colonic segments by ELISA. The results represent the mean of the cytokine secretion in individual mice/group ± SEM. * p<0.05, ** p<0.01 and *** p<0.001 (n = 4–5 animals/group).

Mentions: Considering that TNBS instillation in mice induced an intense colon inflammation, we analyzed the local secretion of IL-1β, IL-6 and TNF-α. The results showed high levels of these pro-inflammatory cytokines in homogenates of colonic tissue from the TNBS group compared with the control groups (ETOH and ETOH/CTX), reflecting the state of acute intestinal inflammation (Fig 2A, 2B and 2C). However, reduced secretion of these cytokines was observed in TNBS-mice that received CTX as compared with the untreated TNBS group (Fig 2A–2C).


Crotoxin from Crotalus durissus terrificus is able to down-modulate the acute intestinal inflammation in mice.

Almeida Cde S, Andrade-Oliveira V, Câmara NO, Jacysyn JF, Faquim-Mauro EL - PLoS ONE (2015)

Secretion of pro-inflammatory cytokines in colonic tissue homogenates of TNBS-mice treated or not with CTX.Production of IL-1β (A), IL-6 (B) and TNF-α (C) was measured in homogenates of colonic segments by ELISA. The results represent the mean of the cytokine secretion in individual mice/group ± SEM. * p<0.05, ** p<0.01 and *** p<0.001 (n = 4–5 animals/group).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390225&req=5

pone.0121427.g002: Secretion of pro-inflammatory cytokines in colonic tissue homogenates of TNBS-mice treated or not with CTX.Production of IL-1β (A), IL-6 (B) and TNF-α (C) was measured in homogenates of colonic segments by ELISA. The results represent the mean of the cytokine secretion in individual mice/group ± SEM. * p<0.05, ** p<0.01 and *** p<0.001 (n = 4–5 animals/group).
Mentions: Considering that TNBS instillation in mice induced an intense colon inflammation, we analyzed the local secretion of IL-1β, IL-6 and TNF-α. The results showed high levels of these pro-inflammatory cytokines in homogenates of colonic tissue from the TNBS group compared with the control groups (ETOH and ETOH/CTX), reflecting the state of acute intestinal inflammation (Fig 2A, 2B and 2C). However, reduced secretion of these cytokines was observed in TNBS-mice that received CTX as compared with the untreated TNBS group (Fig 2A–2C).

Bottom Line: Crotoxin (CTX) is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect.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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunopathology, Butantan Institute, São Paulo, São Paulo, Brazil.

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-α, IL-1β 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-β, prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) 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.

No MeSH data available.


Related in: MedlinePlus