PMID- 24015275
OWN - NLM
STAT- MEDLINE
DCOM- 20140331
LR  - 20220409
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 8
DP  - 2013
TI  - Interleukin 13 and serotonin: linking the immune and endocrine systems in murine 
      models of intestinal inflammation.
PG  - e72774
LID - 10.1371/journal.pone.0072774 [doi]
LID - e72774
AB  - 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.
FAU - Shajib, Md Sharif
AU  - Shajib MS
AD  - Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada ; 
      Department of Pathology & Molecular Medicine, McMaster University, Hamilton, 
      Ontario, Canada.
FAU - Wang, Huaqing
AU  - Wang H
FAU - Kim, Janice J
AU  - Kim JJ
FAU - Sunjic, Ivana
AU  - Sunjic I
FAU - Ghia, Jean-Eric
AU  - Ghia JE
FAU - Denou, Emmanuel
AU  - Denou E
FAU - Collins, Matthew
AU  - Collins M
FAU - Denburg, Judah A
AU  - Denburg JA
FAU - Khan, Waliul I
AU  - Khan WI
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130828
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Benzenesulfonates)
RN  - 0 (Interleukin-13)
RN  - 12379-41-8 (dinitrobenzenesulfonic acid)
RN  - 333DO1RDJY (Serotonin)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
MH  - Animals
MH  - Benzenesulfonates/toxicity
MH  - Colitis/chemically induced/genetics/immunology/*metabolism/pathology
MH  - Dextran Sulfate/toxicity
MH  - Disease Models, Animal
MH  - Endocrine System/immunology/*metabolism/pathology
MH  - Interleukin-13/genetics/immunology/*metabolism/pharmacology
MH  - Macrophages, Peritoneal/immunology/*metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Serotonin/genetics/immunology/metabolism/pharmacology
PMC - PMC3755966
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/09/10 06:00
MHDA- 2014/04/01 06:00
PMCR- 2013/08/28
CRDT- 2013/09/10 06:00
PHST- 2013/04/07 00:00 [received]
PHST- 2013/07/12 00:00 [accepted]
PHST- 2013/09/10 06:00 [entrez]
PHST- 2013/09/10 06:00 [pubmed]
PHST- 2014/04/01 06:00 [medline]
PHST- 2013/08/28 00:00 [pmc-release]
AID - PONE-D-13-14207 [pii]
AID - 10.1371/journal.pone.0072774 [doi]
PST - epublish
SO  - PLoS One. 2013 Aug 28;8(8):e72774. doi: 10.1371/journal.pone.0072774. eCollection 
      2013.