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Article

Effect of tofacitinib on the phenotype and activity of Caco‑2 cells in a model of inflammatory bowel disease

  • Authors:
    • Estera Skudrzyk
    • Łukasz Bułdak
    • Grzegorz Machnik
    • Bogusław Okopień
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia, 40‑752 Katowice, Poland
  • Article Number: 152
    |
    Published online on: February 20, 2024
       https://doi.org/10.3892/etm.2024.12440
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Abstract

Reports have indicated that autoimmune bowel disorders affect an increasing number of people on every continent; therefore, it is important to better understand inflammatory bowel disease (IBD) and to explore new treatment options for patients suffering from it. Research has indicated the important role of enterocytes in IBD. Understanding the role of the intestinal epithelium in the pathogenesis of IBD may contribute to a better understanding of the inflammatory processes and aid in the identification of potential therapeutic treatments. The present study aimed to evaluate the effects of tofacitinib on Caco‑2 cells cultured in an inflammatory environment induced using cytokines naturally found in patients with ulcerative colitis. Tofacitinib is an orally administered inhibitor of Janus kinases (JAKs) which, by modifying the JAK/STAT signaling pathway, reduces the effect of inflammatory cytokines in the gut. Caco‑2 cells were used to model the intestinal epithelium and the culture conditions included the proinflammatory cytokine TNFα and tofacitinib. At the end of the culture period, enzymes involved in oxidative stress (superoxide dismutase 1, catalase, nicotinamide adenine dinucleotide phosphate), a marker of apoptosis (Bcl‑2) and a key player in intracellular inflammatory signaling (nuclear factor κB) were assessed by quantitative PCR and western blotting. The in vitro phenotype of Caco‑2 cells exposed to an inflammatory environment was observed to be similar to that observed in ulcerative colitis. Notably, tofacitinib was able to improve TNFα‑induced changes in an in vitro model of ulcerative colitis, and a reduction in the activity of enzymes associated with oxidative stress was observed. In addition, tofacitinib‑induced upregulation of Bcl‑2 and claudin‑1 may contribute to the beneficial effects of tofacitinib on the intestinal epithelium. Tofacitinib appears to have a protective effect on Caco‑2 cells. Notably, in the present study, exposure to TNFα stimulated oxidative stress and apoptotic effects, and disrupted intercellular connectivity. The addition of tofacitinib decreased the activity of the examined parameters of oxidative and apoptotic stress, while increasing the activity of the parameter examined to evaluate the degree of intercellular connections. In conclusion, the inhibitory effects of tofacitinib on oxidative stress, as well as its anti‑apoptotic and regenerative effects, provide important information regarding the positive effect of tofacitinib on Caco‑2 cells, and therefore constitute potential information about the beneficial effect of the evaluated drug in UC.
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Copy and paste a formatted citation
Spandidos Publications style
Skudrzyk E, Bułdak Ł, Machnik G and Okopień B: Effect of tofacitinib on the phenotype and activity of Caco‑2 cells in a model of inflammatory bowel disease. Exp Ther Med 27: 152, 2024.
APA
Skudrzyk, E., Bułdak, Ł., Machnik, G., & Okopień, B. (2024). Effect of tofacitinib on the phenotype and activity of Caco‑2 cells in a model of inflammatory bowel disease. Experimental and Therapeutic Medicine, 27, 152. https://doi.org/10.3892/etm.2024.12440
MLA
Skudrzyk, E., Bułdak, Ł., Machnik, G., Okopień, B."Effect of tofacitinib on the phenotype and activity of Caco‑2 cells in a model of inflammatory bowel disease". Experimental and Therapeutic Medicine 27.4 (2024): 152.
Chicago
Skudrzyk, E., Bułdak, Ł., Machnik, G., Okopień, B."Effect of tofacitinib on the phenotype and activity of Caco‑2 cells in a model of inflammatory bowel disease". Experimental and Therapeutic Medicine 27, no. 4 (2024): 152. https://doi.org/10.3892/etm.2024.12440
Copy and paste a formatted citation
x
Spandidos Publications style
Skudrzyk E, Bułdak Ł, Machnik G and Okopień B: Effect of tofacitinib on the phenotype and activity of Caco‑2 cells in a model of inflammatory bowel disease. Exp Ther Med 27: 152, 2024.
APA
Skudrzyk, E., Bułdak, Ł., Machnik, G., & Okopień, B. (2024). Effect of tofacitinib on the phenotype and activity of Caco‑2 cells in a model of inflammatory bowel disease. Experimental and Therapeutic Medicine, 27, 152. https://doi.org/10.3892/etm.2024.12440
MLA
Skudrzyk, E., Bułdak, Ł., Machnik, G., Okopień, B."Effect of tofacitinib on the phenotype and activity of Caco‑2 cells in a model of inflammatory bowel disease". Experimental and Therapeutic Medicine 27.4 (2024): 152.
Chicago
Skudrzyk, E., Bułdak, Ł., Machnik, G., Okopień, B."Effect of tofacitinib on the phenotype and activity of Caco‑2 cells in a model of inflammatory bowel disease". Experimental and Therapeutic Medicine 27, no. 4 (2024): 152. https://doi.org/10.3892/etm.2024.12440
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