Role of mast cells in inflammatory bowel disease and inflammation-associated colorectal neoplasia in IL-10-deficient mice.


Autoria(s): Chichlowski, M; Westwood, GS; Abraham, SN; Hale, LP
Data(s)

17/08/2010

Identificador

http://www.ncbi.nlm.nih.gov/pubmed/20808919

PLoS One, 2010, 5 (8), pp. e12220 - ?

http://hdl.handle.net/10161/4564

1932-6203

http://hdl.handle.net/10161/4564

Idioma(s)

ENG

en_US

Relação

PLoS One

10.1371/journal.pone.0012220

Plos One

Tipo

Journal Article

Cobertura

United States

Resumo

BACKGROUND: Inflammatory bowel disease (IBD) is hypothesized to result from stimulation of immune responses against resident intestinal bacteria within a genetically susceptible host. Mast cells may play a critical role in IBD pathogenesis, since they are typically located just beneath the intestinal mucosal barrier and can be activated by bacterial antigens. METHODOLOGY/PRINCIPAL FINDINGS: This study investigated effects of mast cells on inflammation and associated neoplasia in IBD-susceptible interleukin (IL)-10-deficient mice with and without mast cells. IL-10-deficient mast cells produced more pro-inflammatory cytokines in vitro both constitutively and when triggered, compared with wild type mast cells. However despite this enhanced in vitro response, mast cell-sufficient Il10(-/-) mice actually had decreased cecal expression of tumor necrosis factor (TNF) and interferon (IFN)-gamma mRNA, suggesting that mast cells regulate inflammation in vivo. Mast cell deficiency predisposed Il10(-/-) mice to the development of spontaneous colitis and resulted in increased intestinal permeability in vivo that preceded the development of colon inflammation. However, mast cell deficiency did not affect the severity of IBD triggered by non-steroidal anti-inflammatory agents (NSAID) exposure or helicobacter infection that also affect intestinal permeability. CONCLUSIONS/SIGNIFICANCE: Mast cells thus appear to have a primarily protective role within the colonic microenvironment by enhancing the efficacy of the mucosal barrier. In addition, although mast cells were previously implicated in progression of sporadic colon cancers, mast cells did not affect the incidence or severity of colonic neoplasia in this inflammation-associated model.

Formato

e12220 - ?

Palavras-Chave #Animals #Colorectal Neoplasms #Disease Susceptibility #Helicobacter #Humans #Inflammation #Inflammation Mediators #Inflammatory Bowel Diseases #Interleukin-10 #Intestinal Mucosa #Mast Cells #Mice #Piroxicam