PMID- 36002565
OWN - NLM
STAT- MEDLINE
DCOM- 20220826
LR  - 20230124
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Aug 24
TI  - Jejunum-derived NF-kappaB reporter organoids as 3D models for the study of 
      TNF-alpha-induced inflammation.
PG  - 14425
LID - 10.1038/s41598-022-18556-3 [doi]
LID - 14425
AB  - Inflammation is an important process for epithelial barrier protection but when 
      uncontrolled, it can also lead to tissue damage. The nuclear factor-kappa light 
      chain enhancer of activated B cells (NF-kappaB) signaling pathway is particularly 
      relevant in the intestine, as it seems to play a dual role. Whereas NF-kappaB 
      protects intestinal epithelium against various noxious stimuli, the same pathway 
      mediates intestinal inflammatory diseases by inducing pro-inflammatory gene 
      expression. The availability of appropriate in vitro models of the intestinal 
      epithelium is crucial for further understanding the contribution of NF-kappaB in 
      physiological and pathological processes and advancing in the development of 
      drugs and therapies against gut diseases. Here we established, characterized, and 
      validated three-dimensional cultures of intestinal organoids obtained from 
      biopsies of NF-kappaB-RE-Luc mice. The NF-kappaB-RE-Luc intestinal organoids derived from 
      different intestine regions recreated the cellular composition of the tissue and 
      showed a reporter responsiveness similar to the in vivo murine model. When 
      stimulated with TNF-alpha, jejunum-derived NF-kappaB-RE-Luc-reporter organoids, provided 
      a useful model to evaluate the anti-inflammatory effects of natural and synthetic 
      compounds. These reporter organoids are valuable tools to explore the epithelial 
      TNF-alpha-induced NF-kappaB contribution in the small intestine, being a reliable 
      alternative method while helping to reduce the use of laboratory animals for 
      experimentation.
CI  - (c) 2022. The Author(s).
FAU - Daghero, Hellen
AU  - Daghero H
AD  - Cell Biology Unit, Institut Pasteur de Montevideo, Mataojo 2020, 11400, 
      Montevideo, Uruguay.
FAU - Doffe, Flora
AU  - Doffe F
AD  - INSERM, UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, 
      Faculty of Medecine, University Paris-Saclay, 94805, Villejuif, France.
FAU - Varela, Belen
AU  - Varela B
AD  - Pathology Unit, Department of Pathobiology, Faculty of Veterinary, Universidad de 
      la Republica, Route 8, Km. 18 and Route 102, CP 13000, Montevideo, Uruguay.
FAU - Yozzi, Victoria
AU  - Yozzi V
AD  - Pathology Unit, Department of Pathobiology, Faculty of Veterinary, Universidad de 
      la Republica, Route 8, Km. 18 and Route 102, CP 13000, Montevideo, Uruguay.
FAU - Verdes, Jose Manuel
AU  - Verdes JM
AD  - Pathology Unit, Department of Pathobiology, Faculty of Veterinary, Universidad de 
      la Republica, Route 8, Km. 18 and Route 102, CP 13000, Montevideo, Uruguay.
FAU - Crispo, Martina
AU  - Crispo M
AD  - Laboratory Animal Biotechnology Unit, Institut Pasteur de Montevideo, Mataojo 
      2020, 11400, Montevideo, Uruguay.
FAU - Bollati-Fogolin, Mariela
AU  - Bollati-Fogolin M
AD  - Cell Biology Unit, Institut Pasteur de Montevideo, Mataojo 2020, 11400, 
      Montevideo, Uruguay. mbollati@pasteur.edu.uy.
FAU - Pagotto, Romina
AU  - Pagotto R
AD  - Cell Biology Unit, Institut Pasteur de Montevideo, Mataojo 2020, 11400, 
      Montevideo, Uruguay. pagotto@pasteur.edu.uy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220824
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Inflammation/metabolism
MH  - Jejunum/metabolism
MH  - Mice
MH  - *NF-kappa B/metabolism
MH  - Organoids/metabolism
MH  - *Tumor Necrosis Factor-alpha/metabolism
PMC - PMC9829906
COIS- The authors declare no competing interests.
EDAT- 2022/08/25 06:00
MHDA- 2022/08/27 06:00
PMCR- 2022/08/24
CRDT- 2022/08/24 23:24
PHST- 2021/08/23 00:00 [received]
PHST- 2022/08/16 00:00 [accepted]
PHST- 2022/08/24 23:24 [entrez]
PHST- 2022/08/25 06:00 [pubmed]
PHST- 2022/08/27 06:00 [medline]
PHST- 2022/08/24 00:00 [pmc-release]
AID - 10.1038/s41598-022-18556-3 [pii]
AID - 18556 [pii]
AID - 10.1038/s41598-022-18556-3 [doi]
PST - epublish
SO  - Sci Rep. 2022 Aug 24;12(1):14425. doi: 10.1038/s41598-022-18556-3.