Gastric mucosal interleukin-17 and -18 mRNA expression in Helicobacter pylori-induced Mongolian gerbils.
Helicobacter pylori infection causes characteristic mucosal infiltration of inflammatory cells, resulting in the development of peptic ulcers and gastric cancer in approximately 10% of cases. Different clinical expressions of the infection may reflect different patterns of cytokine expression. Interleukin (IL)-1ss, tumor necrosis factor (TNF)-alpha, IL-17, and IL-18 have been reported to be involved in H. pylori-induced gastric mucosal inflammation, but the details and relation to different patterns of inflammation remain unclear. Moreover, the proinflammatory virulence factor outer inflammatory protein (OipA) was reported to be associated with gastric mucosal inflammatory cytokine levels. To clarify these findings, Mongolian gerbils were infected for up to 12 months with wild-type H. pylori 7.13 or with isogenic oipA mutants for 3 months, and mucosal cytokines (IL-1ss, IL-17, IL-18, and TNF-alpha) mRNA levels were then assessed using real-time RT-PCR. Antral mucosal IL-1beta and IL-18 mRNA levels peaked 1 month after infection, whereas the peak of TNF-alpha mRNA was at 6-12 months; IL-17 levels peaked at 12 months. The inflammatory cell infiltration and mRNA levels of all cytokines studied were significantly lower in oipA mutants than in wild-type-infected gerbils. Mucosal IL-1ss, IL-17, and TNF-alpha expression, but not that of IL-18, were significantly associated with the grade of inflammatory cell infiltration. The pattern of increased inflammatory cytokines differed relative to the phase of the infection and pattern of inflammation. OipA appears to play a role in IL-1ss, IL-17, and TNF-alpha expression and the resulting inflammation.
Sugimoto
Mitsushige
M
Department of Medicine - Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA.
Ohno
Tomoyuki
T
Graham
David Y
DY
Yamaoka
Yoshio
Y
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D005753:Gastric Mucosa / Q000276:immunology*; D005756:Gastritis / Q000276:immunology; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori; D020381:Interleukin-17 / Q000235:genetics*; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis*; D013276:Stomach Ulcer / Q000276:immunology
D001425:Bacterial Outer Membrane Proteins; D020381:Interleukin-17; D020382:Interleukin-18; C526444:OipA protein, Helicobacter pylori; D012333:RNA, Messenger
Int J Mol Med. 2007 Nov;20(5):717-23
17912466
Gut. 1997 Oct;41(4):442-51
9391240
Nature. 1995 Nov 2;378(6552):88-91
7477296
Scand J Gastroenterol. 1995 Dec;30(12):1153-9
9053967
Hum Pathol. 1996 Jan;27(1):35-41
8543308
J Clin Invest. 1999 May;103(9):1345-52
10225978
Dig Dis Sci. 2003 Nov;48(11):2139-46
14705819
Ann N Y Acad Sci. 2002 Jun;963:326-8
12095959
Cancer Res. 2008 Jan 15;68(2):379-87
18199531
J Infect Dis. 2001 Feb 15;183(4):620-7
11170988
J Infect Dis. 2006 Nov 15;194(10):1346-55
17054063
Infect Immun. 2005 Apr;73(4):2205-12
15784564
Am J Pathol. 1999 Mar;154(3):951-60
10079274
N Engl J Med. 2001 Sep 13;345(11):784-9
11556297
J Gastroenterol Hepatol. 2007 Jan;22(1):51-9
17201881
Gastroenterology. 1998 Mar;114(3):482-92
9496938
Int J Cancer. 1985 Feb 15;35(2):173-7
3871738
J Infect Dis. 2008 Jun 15;197(12):1752-61
18442334
Helicobacter. 2008 Dec;13(6):518-24
19166417
Gut. 2001 Jun;48(6):765-73
11358893
J Clin Microbiol. 2001 Apr;39(4):1283-8
11283042
Clin Immunol. 2008 Jun;127(3):385-93
18373953
Cancer Res. 2008 May 15;68(10):3915-23
18483277
Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1920-8
17035400
Cancer. 2001 Oct 15;92(8):2050-5
11596019
Gastroenterology. 2001 Oct;121(4):823-9
11606496
Gastroenterology. 2004 Apr;126(4):1030-43
15057743
Br J Cancer. 1998 Jul;78(2):263-6
9683304
World J Gastroenterol. 2005 Oct 28;11(40):6305-11
16419159
Gastroenterology. 1998 Sep;115(3):642-8
9721161
Gastroenterology. 2002 Aug;123(2):414-24
12145793
J Clin Pathol. 2002 Oct;55(10):770-3
12354805
J Immunol. 2000 Nov 1;165(9):5332-7
11046068
J Immunol. 1993 Jun 15;150(12):5445-56
8390535
Nature. 2000 Mar 23;404(6776):398-402
10746728
J Immunol. 2008 Jan 15;180(2):1207-16
18178861
Immunity. 2004 Oct;21(4):467-76
15485625
Int J Cancer. 1994 May 1;57(3):324-9
8168991
Infect Immun. 2004 Sep;72(9):5019-26
15321994
J Exp Med. 2000 Dec 4;192(11):1601-10
11104802
Gastroenterology. 2002 Dec;123(6):1793-803
12454835
J Gastroenterol Hepatol. 2007 Sep;22(9):1443-9
17716348
Gastroenterology. 2003 May;124(5):1193-201
12730860
J Clin Microbiol. 2004 May;42(5):2279-81
15131212
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7533-8
10852959
J Gastroenterol. 1996 Oct;31(5):755-7
8887049