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Worm proteins of Schistosoma mansoni reduce the severity of experimental chronic colitis in mice by suppressing colonic proinflammatory immune responses.

Heylen M, Ruyssers NE, De Man JG, Timmermans JP, Pelckmans PA, Moreels TG, De Winter BY - PLoS ONE (2014)

Bottom Line: The therapeutic potential of the preventive SmSWP treatment (started before colitis was established), was less pronounced compared with the curative SmSWP treatment but still resulted in an improved clinical disease score, body weight loss, colon length and microscopic inflammation score.Moreover, the effect of SmSWP appeared to be a local colonic phenomenon, since the flow cytometric T cell characterization of the mesenteric lymph nodes and the cytokine measurements in the serum did not reveal any effect of SmSWP treatment.In conclusion, SmSWP treatment reduced the severity of colitis in the adoptive transfer mouse model via the suppression of proinflammatory cytokines and the induction of an anti-inflammatory response in the colon.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.

ABSTRACT
Although helminthic therapy as a possible new option to treat inflammatory bowel disease is a well-established concept by now, the search for immunomodulatory helminth-derived compounds and their mechanisms of action is still ongoing. We investigated the therapeutic potential and the underlying immunological mechanisms of Schistosoma mansoni soluble worm proteins (SmSWP) in an adoptive T cell transfer mouse model of chronic colitis. Both a curative and a preventive treatment protocol were included in this study. The curative administration of SmSWP (started when colitis was established), resulted in a significant improvement of the clinical disease score, colonoscopy, macroscopic and microscopic inflammation score, colon length and myeloperoxidase activity. The therapeutic potential of the preventive SmSWP treatment (started before colitis was established), was less pronounced compared with the curative SmSWP treatment but still resulted in an improved clinical disease score, body weight loss, colon length and microscopic inflammation score. Both the curative and preventive SmSWP treatment downregulated the mRNA expression of the proinflammatory cytokines IFN-γ and IL-17A and upregulated the mRNA expression of the anti-inflammatory cytokine IL-4 in the colon at the end of the experiment. This colonic immunomodulatory effect of SmSWP could not be confirmed at the protein level. Moreover, the effect of SmSWP appeared to be a local colonic phenomenon, since the flow cytometric T cell characterization of the mesenteric lymph nodes and the cytokine measurements in the serum did not reveal any effect of SmSWP treatment. In conclusion, SmSWP treatment reduced the severity of colitis in the adoptive transfer mouse model via the suppression of proinflammatory cytokines and the induction of an anti-inflammatory response in the colon.

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Effect of curative treatment with SmSWP on inflammatory parameters.Effect on clinical disease score (A), body weight (B), colonoscopic score (C), macroscopic inflammation score (D), colon length (E), microscopic inflammation score (F) and MPO activity (G). Data are presented as mean ± SEM. Generalized Estimations Equations was used to analyze the evolution of the body weight, the clinical disease score and colonoscopic score over time and an LSD post-hoc analysis was applied. One-way ANOVA with LSD post-hoc test was used to compare the results of macroscopic and microscopic scores, colon length and MPO activity between groups. #: P≤0.05, significantly different from CONTROL group; *: P≤0.05, significant difference between the COLITIS and COLITIS+curSmSWP groups; §: P≤0.05, significant increase in score between week 4 and week 6 for the COLITIS group; “n” representing the number of mice. Abbreviations: cur: curative; LSD: least significant difference; MPO: myeloperoxidase; SEM: standard error of the mean; SmSWP: Schistosoma mansoni soluble worm proteins.
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pone-0110002-g003: Effect of curative treatment with SmSWP on inflammatory parameters.Effect on clinical disease score (A), body weight (B), colonoscopic score (C), macroscopic inflammation score (D), colon length (E), microscopic inflammation score (F) and MPO activity (G). Data are presented as mean ± SEM. Generalized Estimations Equations was used to analyze the evolution of the body weight, the clinical disease score and colonoscopic score over time and an LSD post-hoc analysis was applied. One-way ANOVA with LSD post-hoc test was used to compare the results of macroscopic and microscopic scores, colon length and MPO activity between groups. #: P≤0.05, significantly different from CONTROL group; *: P≤0.05, significant difference between the COLITIS and COLITIS+curSmSWP groups; §: P≤0.05, significant increase in score between week 4 and week 6 for the COLITIS group; “n” representing the number of mice. Abbreviations: cur: curative; LSD: least significant difference; MPO: myeloperoxidase; SEM: standard error of the mean; SmSWP: Schistosoma mansoni soluble worm proteins.

Mentions: CONTROL mice showed no clinical signs of illness and gained weight during the treatment period (Figure 3A, B). The clinical disease score of COLITIS mice increased significantly over time, whereas the clinical disease score of COLITIS+curSmSWP mice remained stable during the treatment period (i.e. from week 4 to week 6) and was significantly lower than the score of COLITIS mice at week 6 (Figure 3A). The curative administration of SmSWP had no effect on the body weight, as both COLITIS and COLITIS+curSmSWP mice lost weight during the treatment period (Figure 3B).


Worm proteins of Schistosoma mansoni reduce the severity of experimental chronic colitis in mice by suppressing colonic proinflammatory immune responses.

Heylen M, Ruyssers NE, De Man JG, Timmermans JP, Pelckmans PA, Moreels TG, De Winter BY - PLoS ONE (2014)

Effect of curative treatment with SmSWP on inflammatory parameters.Effect on clinical disease score (A), body weight (B), colonoscopic score (C), macroscopic inflammation score (D), colon length (E), microscopic inflammation score (F) and MPO activity (G). Data are presented as mean ± SEM. Generalized Estimations Equations was used to analyze the evolution of the body weight, the clinical disease score and colonoscopic score over time and an LSD post-hoc analysis was applied. One-way ANOVA with LSD post-hoc test was used to compare the results of macroscopic and microscopic scores, colon length and MPO activity between groups. #: P≤0.05, significantly different from CONTROL group; *: P≤0.05, significant difference between the COLITIS and COLITIS+curSmSWP groups; §: P≤0.05, significant increase in score between week 4 and week 6 for the COLITIS group; “n” representing the number of mice. Abbreviations: cur: curative; LSD: least significant difference; MPO: myeloperoxidase; SEM: standard error of the mean; SmSWP: Schistosoma mansoni soluble worm proteins.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196959&req=5

pone-0110002-g003: Effect of curative treatment with SmSWP on inflammatory parameters.Effect on clinical disease score (A), body weight (B), colonoscopic score (C), macroscopic inflammation score (D), colon length (E), microscopic inflammation score (F) and MPO activity (G). Data are presented as mean ± SEM. Generalized Estimations Equations was used to analyze the evolution of the body weight, the clinical disease score and colonoscopic score over time and an LSD post-hoc analysis was applied. One-way ANOVA with LSD post-hoc test was used to compare the results of macroscopic and microscopic scores, colon length and MPO activity between groups. #: P≤0.05, significantly different from CONTROL group; *: P≤0.05, significant difference between the COLITIS and COLITIS+curSmSWP groups; §: P≤0.05, significant increase in score between week 4 and week 6 for the COLITIS group; “n” representing the number of mice. Abbreviations: cur: curative; LSD: least significant difference; MPO: myeloperoxidase; SEM: standard error of the mean; SmSWP: Schistosoma mansoni soluble worm proteins.
Mentions: CONTROL mice showed no clinical signs of illness and gained weight during the treatment period (Figure 3A, B). The clinical disease score of COLITIS mice increased significantly over time, whereas the clinical disease score of COLITIS+curSmSWP mice remained stable during the treatment period (i.e. from week 4 to week 6) and was significantly lower than the score of COLITIS mice at week 6 (Figure 3A). The curative administration of SmSWP had no effect on the body weight, as both COLITIS and COLITIS+curSmSWP mice lost weight during the treatment period (Figure 3B).

Bottom Line: The therapeutic potential of the preventive SmSWP treatment (started before colitis was established), was less pronounced compared with the curative SmSWP treatment but still resulted in an improved clinical disease score, body weight loss, colon length and microscopic inflammation score.Moreover, the effect of SmSWP appeared to be a local colonic phenomenon, since the flow cytometric T cell characterization of the mesenteric lymph nodes and the cytokine measurements in the serum did not reveal any effect of SmSWP treatment.In conclusion, SmSWP treatment reduced the severity of colitis in the adoptive transfer mouse model via the suppression of proinflammatory cytokines and the induction of an anti-inflammatory response in the colon.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.

ABSTRACT
Although helminthic therapy as a possible new option to treat inflammatory bowel disease is a well-established concept by now, the search for immunomodulatory helminth-derived compounds and their mechanisms of action is still ongoing. We investigated the therapeutic potential and the underlying immunological mechanisms of Schistosoma mansoni soluble worm proteins (SmSWP) in an adoptive T cell transfer mouse model of chronic colitis. Both a curative and a preventive treatment protocol were included in this study. The curative administration of SmSWP (started when colitis was established), resulted in a significant improvement of the clinical disease score, colonoscopy, macroscopic and microscopic inflammation score, colon length and myeloperoxidase activity. The therapeutic potential of the preventive SmSWP treatment (started before colitis was established), was less pronounced compared with the curative SmSWP treatment but still resulted in an improved clinical disease score, body weight loss, colon length and microscopic inflammation score. Both the curative and preventive SmSWP treatment downregulated the mRNA expression of the proinflammatory cytokines IFN-γ and IL-17A and upregulated the mRNA expression of the anti-inflammatory cytokine IL-4 in the colon at the end of the experiment. This colonic immunomodulatory effect of SmSWP could not be confirmed at the protein level. Moreover, the effect of SmSWP appeared to be a local colonic phenomenon, since the flow cytometric T cell characterization of the mesenteric lymph nodes and the cytokine measurements in the serum did not reveal any effect of SmSWP treatment. In conclusion, SmSWP treatment reduced the severity of colitis in the adoptive transfer mouse model via the suppression of proinflammatory cytokines and the induction of an anti-inflammatory response in the colon.

Show MeSH
Related in: MedlinePlus