Turkish Journal of Biology
Abstract
Background/aim: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. We hypothesized that the zonulin inhibitor larazotide acetate (LA), designed to regulate loss of tight junctions between intestinal cells and currently used for the treatment of celiac disease, could also have potential therapeutic value in the treatment of IBD.
Materials and methods: BALB/c enteroids were exposed to dextran sulfate sodium (DSS), tumor necrosis factor-alpha (TNFα), or interferon-gamma (IFNγ) for 48 h to induce an IBD-like environment, followed by treatment with LA. Organoids were assessed for intestinal permeability, viability, and expression of the zonulin (Hp), occludin (Ocln), zonula occludens-1 (Zo1), and intestinal stem cell marker (Lgr5) genes.
Results: Enteroids harbored Lgr5+ intestinal stem cells, Muc2+ goblet cells, chromogranin A+ enteroendocrine cells, and lysozyme+ Paneth cells. DSS-, TNFα-, or IFNγ-treated enteroids displayed increased intestinal permeability and loss of epithelial barrier function. While DSS activated apoptotic pathways, exposure to high doses of TNFα and IFNγ resulted in necrosis. DSS-related RNA degradation prevented the assessment of its effects on gene expression in enteroids. Treatment with TNFα, but not IFNγ, induced an increase in zonulin (Hp) expression that could be counteracted by LA.
Conclusion: IBD can be mimicked in vitro best using TNFα. LA showed potential for the treatment of IBD induced by TNFα, but it should be used with caution in highly inflammatory environments.
Author ORCID Identifier
SEMA NUR GÜR: 0009-0006-4268-9979
BURCU PERVİN: 0000-0002-5866-0955
MEHMET EMİN ŞEKER: 0000-0002-8240-5938
FATİMA AERTS KAYA: 0000-0002-9583-8572
DOI
10.55730/1300-0152.2979
Keywords
Inflammatory bowel disease, tumor necrosis factor-alpha, interferon-gamma, zonulin, larazotide acetate
First Page
355
Last Page
363
Publisher
The Scientific and Technological Research Council of Türkiye (TÜBİTAK)
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
GÜR, S, PERVİN, B, ŞEKER, M, & AERTS KAYA, F (2026). Comparison of TNFα, IFNγ, and DSS in modeling inflammatory bowel disease in murine enteroids and assessment of the role of zonulin inhibitor larazotide acetate. Turkish Journal of Biology 50 (5): 355-363. https://doi.org/10.55730/1300-0152.2979
