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


RESULTS
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
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.
Chichlowski
Maciej
M
Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America.
Westwood
Greg S
GS
Abraham
Soman N
SN
Hale
Laura P
LP
D000818:Animals; D015179:Colorectal Neoplasms / Q000150:complications* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D004198:Disease Susceptibility; D016998:Helicobacter / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000150:complications; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D010894:Piroxicam / Q000494:pharmacology
D018836:Inflammation Mediators; D016753:Interleukin-10; D010894:Piroxicam
Am J Physiol Gastrointest Liver Physiol. 2001 Jul;281(1):G216-28
11408275
Gastroenterology. 1990 Jul;99(1):119-24
1693122
Gut. 1990 Jul;31(7):791-4
1695160
Nature. 1996 May 2;381(6577):75-7
8609992
Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22381-6
20018751
Nature. 2008 Jul 24;454(7203):445-54
18650915
Gastroenterology. 1997 Sep;113(3):802-7
9287971
Nat Rev Immunol. 2008 Jun;8(6):478-86
18483499
Clin Exp Allergy. 2008 Feb;38(2):338-49
18005184
Nat Immunol. 2003 Dec;4(12):1199-205
14595438
Carcinogenesis. 2008 Apr;29(4):880-6
18258601
Clin Immunol. 2005 Aug;116(2):135-42
15936249
Int J Syst Bacteriol. 1997 Jul;47(3):627-34
9226892
Gut. 1999 Jan;44(1):96-100
9862833
PLoS Med. 2008 Sep 30;5(9):e198
18828669
J Immunol. 2006 Nov 1;177(9):5791-800
17056503
Gut. 2001 Apr;48(4):526-35
11247898
Comp Med. 2008 Dec;58(6):534-41
19149410
Nat Immunol. 2008 Nov;9(11):1215-23
18936782
Gut. 1975 Jul;16(7):559-63
808445
Helicobacter. 2007 Dec;12(6):598-604
18001399
Nature. 1996 May 2;381(6577):77-80
8609993
Am J Pathol. 2008 Dec;173(6):1693-701
18988802
Blood. 1999 Oct 15;94(8):2658-66
10515869
J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):517-23
10482820
J Clin Gastroenterol. 2010 Jan;44(1):e14-9
19525861
Annu Rev Physiol. 2009;71:489-507
19575684
Clin Exp Allergy. 2005 Jan;35(1):82-8
15649271
Semin Immunopathol. 2009 Jul;31(2):185-205
19533134
Ann Intern Med. 1986 Dec;105(6):883-5
3777713
Chem Pharm Bull (Tokyo). 1985 Aug;33(8):3527-9
4085082
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19977-82
18077429
Gastroenterology. 2004 Aug;127(2):635-57
15300595
Am J Physiol Gastrointest Liver Physiol. 2008 Dec;295(6):G1139-49
18927210
Science. 2002 Sep 6;297(5587):1689-92
12215644
J Invest Dermatol. 1991 Mar;96(3):26S-30S; discussion 30S-31S
2002249
Curr Opin Immunol. 2009 Dec;21(6):679-86
19828301
Cell. 1993 Oct 22;75(2):263-74
8402911
Inflamm Bowel Dis. 1999 Nov;5(4):262-70
10579119
Psychoneuroendocrinology. 2008 Oct;33(9):1248-56
18691825
Gut. 1995 Jun;36(6):857-63
7615274
Int Arch Allergy Immunol. 1995 Oct;108(2):127-33
7549499
Inflamm Bowel Dis. 2010 Sep;16(9):1488-95
20222124
Am J Gastroenterol. 2002 Aug;97(8):2000-4
12190167
Gastroenterology. 2003 Mar;124(3):762-77
12612914
Inflamm Bowel Dis. 2005 Dec;11(12):1060-9
16306768
Am J Physiol Gastrointest Liver Physiol. 2001 Sep;281(3):G764-78
11518689
Gastroenterology. 2002 Nov;123(5):1527-42
12404228