Helicobacter pylori regulates iNOS promoter by histone modifications in human gastric epithelial cells

被引:34
作者
Angrisano, Tiziana [1 ]
Lembo, Francesca [2 ]
Peluso, Silvia [1 ]
Keller, Simona [1 ,2 ]
Chiariotti, Lorenzo [1 ,2 ]
Pero, Raffaela [1 ]
机构
[1] Univ Naples Federico II, Fac Sci Biotecnol, Dipartimento Biol & Patol Cellulare & Mol L Calif, I-80131 Naples, Italy
[2] Univ Naples Federico II, Fac Farm, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy
关键词
Helicobacter pylori; Chromatin modifications; iNOS; Gastric cells; NITRIC-OXIDE SYNTHASE; CLINICAL-RELEVANCE; INFECTION; EXPRESSION; DEMETHYLASE; CANCER; GENE;
D O I
10.1007/s00430-011-0227-9
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Inducible nitric oxide synthase (iNOS) expression is altered in gastrointestinal diseases. Helicobacter pylori (Hp) infection may have a critical role in iNOS disregulation. We undertook this study to investigate possible chromatin changes occurring early during iNOS gene activation as a direct consequence of Hp-gastric cells interaction. We show that Hp infection is followed by different expression and chromatin modifications in gastric cells including (1) activation of iNOS gene expression, (2) chromatin changes at iNOS promoter including decreased H3K9 methylation and increased H3 acetylation and H3K4 methylation levels, (3) selective release of methyl-CpG-binding protein 2 from the iNOS promoter. Moreover, we show that Hp-induced activation of iNOS is delayed, but not eliminated, by the treatment with LSD1 inhibitors. Our data suggest a role for specific chromatin-based mechanisms in the control of human iNOS gene expression upon Hp exposure.
引用
收藏
页码:249 / 257
页数:9
相关论文
共 54 条
[1]   LPS-induced IL-8 activation in human intestinal epithelial cells is accompanied by specific histone H3 acetylation and methylation changes [J].
Angrisano, Tiziana ;
Pero, Raffaela ;
Peluso, Silvia ;
Keller, Simona ;
Sacchetti, Silvana ;
Bruni, Carmelo B. ;
Chiariotti, Lorenzo ;
Lembo, Francesca .
BMC MICROBIOLOGY, 2010, 10
[2]   Natural variation in populations of persistently colonizing bacteria affect human host cell phenotype [J].
Aras, RA ;
Lee, Y ;
Kim, SK ;
Israel, D ;
Peek, RM ;
Blaser, MJ .
JOURNAL OF INFECTIOUS DISEASES, 2003, 188 (04) :486-496
[3]   MOSAICISM IN VACUOLATING CYTOTOXIN ALLELES OF HELICOBACTER-PYLORI - ASSOCIATION OF SPECIFIC VACA TYPES WITH CYTOTOXIN PRODUCTION AND PEPTIC-ULCERATION [J].
ATHERTON, JC ;
CAO, P ;
PEEK, RM ;
TUMMURU, MKR ;
BLASER, MJ ;
COVER, TL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (30) :17771-17777
[4]   The complex language of chromatin regulation during transcription [J].
Berger, Shelley L. .
NATURE, 2007, 447 (7143) :407-412
[5]   Endotoxin tolerance disrupts chromatin remodeling and NF-κB transactivation at the IL-1β promoter [J].
Chan, C ;
Li, LW ;
McCall, CE ;
Yoza, CE .
JOURNAL OF IMMUNOLOGY, 2005, 175 (01) :461-468
[6]   Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-κB activation [J].
Chang, YJ ;
Wu, MS ;
Lin, JT ;
Sheu, BS ;
Muta, T ;
Inoue, H ;
Chen, CC .
MOLECULAR PHARMACOLOGY, 2004, 66 (06) :1465-1477
[7]   CHARACTERIZATION OF AND HUMAN SEROLOGIC RESPONSE TO PROTEINS IN HELICOBACTER-PYLORI BROTH CULTURE SUPERNATANTS WITH VACUOLIZING CYTOTOXIN ACTIVITY [J].
COVER, TL ;
DOOLEY, CP ;
BLASER, MJ .
INFECTION AND IMMUNITY, 1990, 58 (03) :603-610
[8]   Epigenetic silencing of cyclooxygenase-2 affects clinical outcome in gastric cancer [J].
de Maat, Michiel F. G. ;
de Velde, Cornelis J. H. van ;
Umetani, Naoyuki ;
de Heer, Pieter ;
Putter, Hein ;
van Hoesel, Anneke Q. ;
Meijer, Gerrit A. ;
van Grieken, Nicole C. ;
Kuppen, Peter J. K. ;
Bilchik, Anton J. ;
Tollenaar, Rob A. E. M. ;
Hoon, Dave S. B. .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (31) :4887-4894
[9]   Regulation of inducible nitric oxide synthase expression by p300 and p50 acetylation [J].
Deng, WG ;
Wu, KK .
JOURNAL OF IMMUNOLOGY, 2003, 171 (12) :6581-6588
[10]  
Erkisi M, 1997, J EXP CLIN CANC RES, V16, P289