Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis.
BACKGROUND
Interleukin (IL)-33 is a cytokine belonging to the IL-1 family. IL-33 has been shown to elicit a Th2-like cytokine response in immune cells. In this study, we investigated IL-33 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for IL-33 expression in human colonic subepithelial myofibroblasts (SEMFs).


METHODS
IL-33 mRNA expression was determined by real-time polymerase chain reaction (PCR). IL-33 expression in the IBD mucosa was evaluated by immunohistochemical methods.


RESULTS
IL-33 mRNA expression was significantly elevated in active lesions from patients with ulcerative colitis (UC), but was not detected in inactive lesions from UC patients or in lesions from patients with either active or inactive Crohn's disease. Colonic SEMFs were identified as a major source of IL-33 in the mucosa. IL-1β and tumor necrosis factor-α (TNF-α) significantly enhanced IL-33 mRNA and protein expression in isolated colonic SEMFs. IL-1β and TNF-α did not affect IL-33 expression in intestinal epithelial cell lines (HT-29 and Caco-2 cells). This IL-1β- and TNF-α-induced IL-33 mRNA expression was mediated by p42/44 mitogen activated protein kinase (MAPK) pathway-dependent activation of nuclear factor (NF)-κB and activator protein (AP)-1.


CONCLUSIONS
IL-33, derived from colonic SEMFs, may play an important role in the pathophysiology of UC.
Kobori
Ayako
A
Department of Medicine, Shiga University of Medical Science, Seta Tukinowa, Otsu, Japan.
Yagi
Yuhki
Y
Imaeda
Hirotsugu
H
Ban
Hiromitsu
H
Bamba
Shigeki
S
Tsujikawa
Tomoyuki
T
Saito
Yasuharu
Y
Fujiyama
Yoshihide
Y
Andoh
Akira
A
D018938:Caco-2 Cells; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000166:cytology / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D019073:HT29 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000008:administration & dosage; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000473:pathology*; D058628:Myofibroblasts / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
C506536:IL33 protein, human; D053583:Interleukin-1beta; D000067596:Interleukin-33; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
Gut. 2010 Apr;59(4):531-41
19996325
Gastroenterology. 1979 Oct;77(4 Pt 2):843-6
467941
J Clin Invest. 2007 Jun;117(6):1538-49
17492053
J Immunol. 2009 Oct 15;183(8):5094-103
19801525
Gastroenterology. 2005 Aug;129(2):550-64
16083712
Am J Physiol. 1997 Dec;273(6):G1341-8
9435560
FEBS Lett. 1995 May 8;364(2):229-33
7750577
Biochem Biophys Res Commun. 2009 Jun 19;384(1):105-9
19393621
J Gastroenterol. 2007 Jan;42(1):16-25
17322989
J Leukoc Biol. 2007 Dec;82(6):1481-90
17881510
FEMS Immunol Med Microbiol. 2008 Aug;53(3):385-94
18625013
Immunity. 2005 Nov;23(5):479-90
16286016
Gene Ther. 2001 Nov;8(22):1682-9
11892835
Nat Rev Immunol. 2003 Jul;3(7):521-33
12876555
J Gastroenterol. 2010;45(1):9-16
19960355
J Cell Mol Med. 2010 Jun;14(6B):1726-39
19508382
J Biol Chem. 1998 Jul 17;273(29):18623-32
9660836
Cell Signal. 2007 Dec;19(12):2487-97
17826033
J Biol Chem. 1995 Nov 17;270(46):27489-94
7499206
Toxicol Lett. 2008 Sep 26;181(2):112-7
18675330
Inflamm Bowel Dis. 2008 Sep;14(9):1175-84
18512248
Inflamm Bowel Dis. 2010 Jul;16(7):1097-107
20014018
J Immunol. 2002 Aug 15;169(4):1683-7
12165487
Am J Physiol Gastrointest Liver Physiol. 2002 Jun;282(6):G1035-44
12016129
J Gastroenterol. 2008;43(1):1-17
18297430
J Immunol. 2002 Jan 15;168(2):861-8
11777983
J Allergy Clin Immunol. 2009 May;123(5):1047-54
19361843
Arterioscler Thromb Vasc Biol. 2000 Oct;20(10):2198-204
11031204
Immunol Lett. 2010 Jan 18;128(1):80-5
19913053
BMJ. 1989 Jan 14;298(6666):82-6
2563951