Limits...
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

Analysis of CD4+FoxP3+ cells and anti-inflammatory mediators in TNBS-mice treated or not with CTX.Cell suspensions were prepared from lamina propria of distinct experimental groups after 4 days of TNBS-induced colitis for the analysis of CD4+FoxP3+ cells by flow cytometry. The samples were prepared from a pool of cells from 4–5 animals/group performed in duplicate. The results are from 2 independent experiments. (A) Representative dot plots of CD4+FoxP3+ cells in the lamina propria obtained from distinct experimental groups. (B) Results of CD4+FoxP3+ cells expressed as a mean of the absolute number of cells in duplicate of 2 independent experiments ± SEM. Secretion of TGF-β (C) and IL-10 (D) in colonic tissue homogenates determined by ELISA. Production of PGE2(E) and LXA4(F) was performed by ELISA in colonic tissue homogenates. The results represent the mean obtained 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
getmorefigures.php?uid=PMC4390225&req=5

pone.0121427.g005: Analysis of CD4+FoxP3+ cells and anti-inflammatory mediators in TNBS-mice treated or not with CTX.Cell suspensions were prepared from lamina propria of distinct experimental groups after 4 days of TNBS-induced colitis for the analysis of CD4+FoxP3+ cells by flow cytometry. The samples were prepared from a pool of cells from 4–5 animals/group performed in duplicate. The results are from 2 independent experiments. (A) Representative dot plots of CD4+FoxP3+ cells in the lamina propria obtained from distinct experimental groups. (B) Results of CD4+FoxP3+ cells expressed as a mean of the absolute number of cells in duplicate of 2 independent experiments ± SEM. Secretion of TGF-β (C) and IL-10 (D) in colonic tissue homogenates determined by ELISA. Production of PGE2(E) and LXA4(F) was performed by ELISA in colonic tissue homogenates. The results represent the mean obtained in individual mice/group ± SEM. * p<0.05, ** p<0.01 and *** p<0.001; (n = 4–5 animals/group).

Mentions: As shown in (Fig 5A, 5B and 5C) an increased CD4+FoxP3+ cell population in lamina propria as well as high production of TGF-β in colonic homogenates was detected in the TNBS group treated with CTX when compared with all other groups. Furthermore, we observed a lower production of IL-10 in the TNBS group compared with all other groups (Fig 5D).


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)

Analysis of CD4+FoxP3+ cells and anti-inflammatory mediators in TNBS-mice treated or not with CTX.Cell suspensions were prepared from lamina propria of distinct experimental groups after 4 days of TNBS-induced colitis for the analysis of CD4+FoxP3+ cells by flow cytometry. The samples were prepared from a pool of cells from 4–5 animals/group performed in duplicate. The results are from 2 independent experiments. (A) Representative dot plots of CD4+FoxP3+ cells in the lamina propria obtained from distinct experimental groups. (B) Results of CD4+FoxP3+ cells expressed as a mean of the absolute number of cells in duplicate of 2 independent experiments ± SEM. Secretion of TGF-β (C) and IL-10 (D) in colonic tissue homogenates determined by ELISA. Production of PGE2(E) and LXA4(F) was performed by ELISA in colonic tissue homogenates. The results represent the mean obtained 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.g005: Analysis of CD4+FoxP3+ cells and anti-inflammatory mediators in TNBS-mice treated or not with CTX.Cell suspensions were prepared from lamina propria of distinct experimental groups after 4 days of TNBS-induced colitis for the analysis of CD4+FoxP3+ cells by flow cytometry. The samples were prepared from a pool of cells from 4–5 animals/group performed in duplicate. The results are from 2 independent experiments. (A) Representative dot plots of CD4+FoxP3+ cells in the lamina propria obtained from distinct experimental groups. (B) Results of CD4+FoxP3+ cells expressed as a mean of the absolute number of cells in duplicate of 2 independent experiments ± SEM. Secretion of TGF-β (C) and IL-10 (D) in colonic tissue homogenates determined by ELISA. Production of PGE2(E) and LXA4(F) was performed by ELISA in colonic tissue homogenates. The results represent the mean obtained in individual mice/group ± SEM. * p<0.05, ** p<0.01 and *** p<0.001; (n = 4–5 animals/group).
Mentions: As shown in (Fig 5A, 5B and 5C) an increased CD4+FoxP3+ cell population in lamina propria as well as high production of TGF-β in colonic homogenates was detected in the TNBS group treated with CTX when compared with all other groups. Furthermore, we observed a lower production of IL-10 in the TNBS group compared with all other groups (Fig 5D).

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