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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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F4/80 positive macrophage infiltration in DSS-induced colitis in WT and IL-13−/− mice.F4/80 positive area, positive stained areas expressed as the percent of the total area. (i) and (ii) Representative micrographs. *Represents statistical significance where p<0.05.
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pone-0072774-g004: F4/80 positive macrophage infiltration in DSS-induced colitis in WT and IL-13−/− mice.F4/80 positive area, positive stained areas expressed as the percent of the total area. (i) and (ii) Representative micrographs. *Represents statistical significance where p<0.05.

Mentions: Reduced 5-HT production in the gut has previously been associated with fewer infiltrating F4/80 positive macrophages in experimental colitis. [10] Consequently, the reduced production of 5-HT observed in the IL-13−/− mice was accompanied by fewer infiltrating macrophages in their colonic segments following DSS treatment in comparison with WT mice (Figure 4). Earlier work in our lab established that, 5-HT stimulation increases IL-1β and IL-6 production by peritoneal resident macrophages. [10]. In the current study, it was observed that macrophages isolated from IL-13−/− mice had dampened cytokine production in comparison to WT mice as revealed when normalized to their respective controls (Table 1) and in culture treatment with 5-HT was able to reverse these effects in IL-13−/− macrophages (Table 1).


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)

F4/80 positive macrophage infiltration in DSS-induced colitis in WT and IL-13−/− mice.F4/80 positive area, positive stained areas expressed as the percent of the total area. (i) and (ii) Representative micrographs. *Represents statistical significance where p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0072774-g004: F4/80 positive macrophage infiltration in DSS-induced colitis in WT and IL-13−/− mice.F4/80 positive area, positive stained areas expressed as the percent of the total area. (i) and (ii) Representative micrographs. *Represents statistical significance where p<0.05.
Mentions: Reduced 5-HT production in the gut has previously been associated with fewer infiltrating F4/80 positive macrophages in experimental colitis. [10] Consequently, the reduced production of 5-HT observed in the IL-13−/− mice was accompanied by fewer infiltrating macrophages in their colonic segments following DSS treatment in comparison with WT mice (Figure 4). Earlier work in our lab established that, 5-HT stimulation increases IL-1β and IL-6 production by peritoneal resident macrophages. [10]. In the current study, it was observed that macrophages isolated from IL-13−/− mice had dampened cytokine production in comparison to WT mice as revealed when normalized to their respective controls (Table 1) and in culture treatment with 5-HT was able to reverse these effects in IL-13−/− macrophages (Table 1).

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