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Interleukin 13 and serotonin: linking the immune and endocrine systems in murine models of intestinal inflammation.

Shajib MS, Wang H, Kim JJ, Sunjic I, Ghia JE, Denou E, Collins M, Denburg JA, Khan WI - PLoS ONE (2013)

Bottom Line: Following DSS administration, significantly lower pro-inflammatory cytokine production and fewer infiltrating macrophages were observed in IL-13-/- mice compared to WT.These results demonstrate that IL-13 plays a critical role in the pathogenesis of experimental colitis and 5-HT is an important mediator of IL-13 driven intestinal inflammation.This study revealed important information on immune-endocrine axis in gut in relation to inflammation which may ultimately lead to better strategy in managing various intestinal inflammatory conditions including inflammatory bowel disease.

View Article: PubMed Central - PubMed

Affiliation: Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada ; Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT

Objective: Infiltration of activated immune cells and increased cytokine production define the immunophenotype of gastrointestinal (GI) inflammation. In addition, intestinal inflammation is accompanied by alteration in the numbers of serotonin (5-hydroxytryptamine; 5-HT) synthesizing enterochromaffin (EC) cells and in 5-HT amount. It has been established that EC cells express interleukin (IL)-13 receptor, additionally IL-13 has been implicated in the pathogenesis of ulcerative colitis. In this study, we investigated the role of IL-13 mediated 5-HT signaling in pathogenesis of colitis.

Methodology: Colitis was induced in IL-13 deficient (IL-13-/-) and wild-type (WT) mice with dextran sulfate sodium (DSS) and dinitrobenzene sulfonic acid (DNBS), as well as in IL-13-/- mice given recombinant mouse IL-13 (rmIL-13) and 5-hydroxytryptamine (5-HTP), the direct precursor of 5-HT.

Principal findings and conclusion: Elevated colonic IL-13 levels were observed in WT mice receiving DSS in comparison to control. IL-13-/- mice administered DSS exhibited significantly reduced severity of colitis compared to WT mice as reflected by macroscopic and histological damage assessments. Following DSS administration, significantly lower pro-inflammatory cytokine production and fewer infiltrating macrophages were observed in IL-13-/- mice compared to WT. The reduced severity of colitis observed in IL-13-/- mice was also accompanied by down-regulation of EC cell numbers and colonic 5-HT content. In addition, increasing colonic 5-HT content by administration of rmIL-13 or 5-HTP exacerbated severity of DSS colitis in IL-13-/- mice. IL-13-/- mice also exhibited reduced severity of DNBS-induced colitis. These results demonstrate that IL-13 plays a critical role in the pathogenesis of experimental colitis and 5-HT is an important mediator of IL-13 driven intestinal inflammation. This study revealed important information on immune-endocrine axis in gut in relation to inflammation which may ultimately lead to better strategy in managing various intestinal inflammatory conditions including inflammatory bowel disease.

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Related in: MedlinePlus

Effects of IL-13 deficiency in DSS-induced colitis.WT and IL-13−/− mice were administered 5% DSS in drinking water to induce colitis. Control mice received water without DSS. (A) Colonic IL-13 levels in WT mice with or without DSS. (B) Disease activity index (DAI). (C) Macroscopic damage score in DSS-induced colitis on day 5 after DSS induced colitis and in mice without colitis. (D) Histological damage assessment on day 5 post-DSS administration. (i) And (ii) Light micrograph of H&E-stained colonic section. DAI data represented as mean ± SEM from 5 mice per group; *represents statistical significance where p<0.05; # significantly lower disease activity in IL-13−/− mice receiving DSS compared to WT mice receiving DSS.
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pone-0072774-g001: Effects of IL-13 deficiency in DSS-induced colitis.WT and IL-13−/− mice were administered 5% DSS in drinking water to induce colitis. Control mice received water without DSS. (A) Colonic IL-13 levels in WT mice with or without DSS. (B) Disease activity index (DAI). (C) Macroscopic damage score in DSS-induced colitis on day 5 after DSS induced colitis and in mice without colitis. (D) Histological damage assessment on day 5 post-DSS administration. (i) And (ii) Light micrograph of H&E-stained colonic section. DAI data represented as mean ± SEM from 5 mice per group; *represents statistical significance where p<0.05; # significantly lower disease activity in IL-13−/− mice receiving DSS compared to WT mice receiving DSS.

Mentions: Colonic IL-13 levels are significantly increased in WT mice on day 5 post-DSS as compared to controls without DSS (Figure 1A). IL-13−/− mice exhibited significantly reduced disease activity compared to WT mice post-DSS administration (Figure 1B). Reduced disease activity was consistently observed in IL-13−/− mice, compared to WT mice, regardless of litters, cages and time of the experiment (Figure S1). IL-13−/− mice also had marked reductions in macroscopic and histological damage scores (Figure 1C and D). Reduction in the severity of DSS colitis was associated with significantly lower MPO activity, as well as reduced IL-1β, IL-6 and IL-17 production in IL-13−/− mice (Figure 2A–D). However, IL-4 levels observed were not significantly different amongst any of the groups (Figure 2E).


Interleukin 13 and serotonin: linking the immune and endocrine systems in murine models of intestinal inflammation.

Shajib MS, Wang H, Kim JJ, Sunjic I, Ghia JE, Denou E, Collins M, Denburg JA, Khan WI - PLoS ONE (2013)

Effects of IL-13 deficiency in DSS-induced colitis.WT and IL-13−/− mice were administered 5% DSS in drinking water to induce colitis. Control mice received water without DSS. (A) Colonic IL-13 levels in WT mice with or without DSS. (B) Disease activity index (DAI). (C) Macroscopic damage score in DSS-induced colitis on day 5 after DSS induced colitis and in mice without colitis. (D) Histological damage assessment on day 5 post-DSS administration. (i) And (ii) Light micrograph of H&E-stained colonic section. DAI data represented as mean ± SEM from 5 mice per group; *represents statistical significance where p<0.05; # significantly lower disease activity in IL-13−/− mice receiving DSS compared to WT mice receiving DSS.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3755966&req=5

pone-0072774-g001: Effects of IL-13 deficiency in DSS-induced colitis.WT and IL-13−/− mice were administered 5% DSS in drinking water to induce colitis. Control mice received water without DSS. (A) Colonic IL-13 levels in WT mice with or without DSS. (B) Disease activity index (DAI). (C) Macroscopic damage score in DSS-induced colitis on day 5 after DSS induced colitis and in mice without colitis. (D) Histological damage assessment on day 5 post-DSS administration. (i) And (ii) Light micrograph of H&E-stained colonic section. DAI data represented as mean ± SEM from 5 mice per group; *represents statistical significance where p<0.05; # significantly lower disease activity in IL-13−/− mice receiving DSS compared to WT mice receiving DSS.
Mentions: Colonic IL-13 levels are significantly increased in WT mice on day 5 post-DSS as compared to controls without DSS (Figure 1A). IL-13−/− mice exhibited significantly reduced disease activity compared to WT mice post-DSS administration (Figure 1B). Reduced disease activity was consistently observed in IL-13−/− mice, compared to WT mice, regardless of litters, cages and time of the experiment (Figure S1). IL-13−/− mice also had marked reductions in macroscopic and histological damage scores (Figure 1C and D). Reduction in the severity of DSS colitis was associated with significantly lower MPO activity, as well as reduced IL-1β, IL-6 and IL-17 production in IL-13−/− mice (Figure 2A–D). However, IL-4 levels observed were not significantly different amongst any of the groups (Figure 2E).

Bottom Line: Following DSS administration, significantly lower pro-inflammatory cytokine production and fewer infiltrating macrophages were observed in IL-13-/- mice compared to WT.These results demonstrate that IL-13 plays a critical role in the pathogenesis of experimental colitis and 5-HT is an important mediator of IL-13 driven intestinal inflammation.This study revealed important information on immune-endocrine axis in gut in relation to inflammation which may ultimately lead to better strategy in managing various intestinal inflammatory conditions including inflammatory bowel disease.

View Article: PubMed Central - PubMed

Affiliation: Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada ; Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT

Objective: Infiltration of activated immune cells and increased cytokine production define the immunophenotype of gastrointestinal (GI) inflammation. In addition, intestinal inflammation is accompanied by alteration in the numbers of serotonin (5-hydroxytryptamine; 5-HT) synthesizing enterochromaffin (EC) cells and in 5-HT amount. It has been established that EC cells express interleukin (IL)-13 receptor, additionally IL-13 has been implicated in the pathogenesis of ulcerative colitis. In this study, we investigated the role of IL-13 mediated 5-HT signaling in pathogenesis of colitis.

Methodology: Colitis was induced in IL-13 deficient (IL-13-/-) and wild-type (WT) mice with dextran sulfate sodium (DSS) and dinitrobenzene sulfonic acid (DNBS), as well as in IL-13-/- mice given recombinant mouse IL-13 (rmIL-13) and 5-hydroxytryptamine (5-HTP), the direct precursor of 5-HT.

Principal findings and conclusion: Elevated colonic IL-13 levels were observed in WT mice receiving DSS in comparison to control. IL-13-/- mice administered DSS exhibited significantly reduced severity of colitis compared to WT mice as reflected by macroscopic and histological damage assessments. Following DSS administration, significantly lower pro-inflammatory cytokine production and fewer infiltrating macrophages were observed in IL-13-/- mice compared to WT. The reduced severity of colitis observed in IL-13-/- mice was also accompanied by down-regulation of EC cell numbers and colonic 5-HT content. In addition, increasing colonic 5-HT content by administration of rmIL-13 or 5-HTP exacerbated severity of DSS colitis in IL-13-/- mice. IL-13-/- mice also exhibited reduced severity of DNBS-induced colitis. These results demonstrate that IL-13 plays a critical role in the pathogenesis of experimental colitis and 5-HT is an important mediator of IL-13 driven intestinal inflammation. This study revealed important information on immune-endocrine axis in gut in relation to inflammation which may ultimately lead to better strategy in managing various intestinal inflammatory conditions including inflammatory bowel disease.

Show MeSH
Related in: MedlinePlus