Faecalibacterium prausnitzii promotes intestinal epithelial IL-18 production through activation of the HIF1α pathway

被引:6
作者
Fagundes, Raphael R. [1 ]
Bravo-Ruiseco, Gabriela [2 ]
Hu, Shixian [1 ]
Kierans, Sarah J. [3 ,4 ]
Weersma, Rinse K. [1 ]
Taylor, Cormac T. [3 ,4 ]
Dijkstra, Gerard [1 ]
Harmsen, Hermie J. M. [2 ]
Faber, Klaas Nico [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol & Infect Prevent, Groningen, Netherlands
[3] Univ Coll Dublin, Sch Med & Med Sci, Dublin, Ireland
[4] Univ Coll Dublin, Conway Inst, Dublin, Ireland
关键词
HIF1; alpha; IL-18; intestine; epithelial-bacteria interaction; HoxBan in vitro coculture system; Faecalibacterium; IBD; INFLAMMATORY-BOWEL-DISEASE; INDUCIBLE FACTOR-I; BARRIER FUNCTION; HYPOXIA; HIF; EXPRESSION; RECEPTOR; BUTYRATE; PERMEABILITY; REPRESSION;
D O I
10.3389/fmicb.2023.1298304
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Introduction Intestinal epithelial cells produce interleukin-18 (IL-18), a key factor in promoting epithelial barrier integrity. Here, we analyzed the potential role of gut bacteria and the hypoxia-inducible factor 1 alpha (HIF1 alpha) pathway in regulating mucosal IL18 expression in inflammatory bowel disease (IBD).Methods Mucosal samples from patients with IBD (n = 760) were analyzed for bacterial composition, IL18 levels and HIF1 alpha pathway activation. Wild-type Caco-2 and CRISPR/Cas9-engineered Caco-2-HIF1A-null cells were cocultured with Faecalibacterium prausnitzii in a "Human oxygen-Bacteria anaerobic" in vitro system and analyzed by RNA sequencing.Results Mucosal IL18 mRNA levels correlated positively with the abundance of mucosal-associated butyrate-producing bacteria, in particular F. prausnitzii, and with HIF1 alpha pathway activation in patients with IBD. HIF1 alpha-mediated expression of IL18, either by a pharmacological agonist (dimethyloxallyl glycine) or F. prausnitzii, was abrogated in Caco-2-HIF1A-null cells.Conclusion Butyrate-producing gut bacteria like F. prausnitzii regulate mucosal IL18 expression in a HIF1 alpha-dependent manner that may aid in mucosal healing in IBD.
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页数:15
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共 78 条
[51]   Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) gene -: Its possible role in the Warburg effect [J].
Minchenko, A ;
Leshchinsky, I ;
Opentanova, I ;
Sang, NL ;
Srinivas, V ;
Armstead, V ;
Caro, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (08) :6183-6187
[52]   Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma [J].
Mo, Zhuomao ;
Yu, Ling ;
Cao, Zhirui ;
Hu, Hao ;
Luo, Shaoju ;
Zhang, Shijun .
FRONTIERS IN GENETICS, 2020, 11
[53]   Inulin-type fructan degradation capacity of Clostridium cluster IV and XIVa butyrate-producing colon bacteria and their associated metabolic outcomes [J].
Moens, F. ;
De Vuyst, L. .
BENEFICIAL MICROBES, 2017, 8 (03) :473-490
[54]   ENDOTOXIN-INDUCED SERUM FACTOR THAT STIMULATES GAMMA INTERFERON-PRODUCTION [J].
NAKAMURA, K ;
OKAMURA, H ;
WADA, M ;
NAGATA, K ;
TAMURA, T .
INFECTION AND IMMUNITY, 1989, 57 (02) :590-595
[55]   Nod-like receptor pyrin domain-containing protein 6 (NLRP6) controls epithelial self-renewal and colorectal carcinogenesis upon injury [J].
Normand, Sylvain ;
Delanoye-Crespin, Anne ;
Bressenot, Aude ;
Huot, Ludovic ;
Grandjean, Teddy ;
Peyrin-Biroulet, Laurent ;
Lemoine, Yves ;
Hot, David ;
Chamaillard, Mathias .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (23) :9601-9606
[56]   Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis [J].
Nowarski, Roni ;
Jackson, Ruaidhri ;
Gagliani, Nicola ;
de Zoete, Marcel R. ;
Palm, Noah W. ;
Bailis, Will ;
Low, Jun Siong ;
Harman, Christian C. D. ;
Graham, Morven ;
Elinav, Eran ;
Flavell, Richard A. .
CELL, 2015, 163 (06) :1444-1456
[57]   CLONING OF A NEW CYTOKINE THAT INDUCES IFN-GAMMA PRODUCTION BY T-CELLS [J].
OKAMURA, H ;
TSUTSUI, H ;
KOMATSU, T ;
YUTSUDO, M ;
HAKURA, A ;
TANIMOTO, T ;
TORIGOE, K ;
OKURA, T ;
NUKADA, Y ;
HATTORI, K ;
AKITA, K ;
NAMBA, M ;
TANABE, F ;
KONISHI, K ;
FUKUDA, S ;
KURIMOTO, M .
NATURE, 1995, 378 (6552) :88-91
[58]   Dual roles of IL-18 in colitis through regulation of the function and quantity of goblet cells [J].
Pu, Zhichen ;
Che, Yuan ;
Zhang, Weiwei ;
Sun, Hui ;
Meng, Tuo ;
Xie, Haitang ;
Cao, Lijuan ;
Hao, Haiping .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2019, 43 (06) :2291-2302
[59]   IER3 Promotes Expansion of Adipose Progenitor Cells in Response to Changes in Distinct Microenvironmental Effectors [J].
Ravaud, Christophe ;
Esteve, David ;
Villageois, Phi ;
Bouloumie, Anne ;
Dani, Christian ;
Ladoux, Annie .
STEM CELLS, 2015, 33 (08) :2564-2573
[60]   Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition [J].
Robinson, Andreas ;
Keely, Simon ;
Karhausen, Joern ;
Gerich, Mark E. ;
Furuta, Glenn T. ;
Colgan, Sean P. .
GASTROENTEROLOGY, 2008, 134 (01) :145-155