Selected Grantee Publications

Proinflammatory Cytokines Suppress Stemness-Related Properties and Expression of Tight Junction in Canine Intestinal Organoids

Nakazawa et al., In Vitro Cellular & Developmental Biology—Animal. 2024.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11419940

Cells in the gastrointestinal tract are exposed to numerous stressors that can promote excessive inflammation, including environmental chemicals and dietary substances. Researchers studied how canine intestinal epithelial cell (IEC)–derived organoids responded to exposure to one of three proinflammatory cytokines; interferon-γ (IFN-γ), tumor necrosis factor-α (TNFα), or interleukin-1β (IL1β). Exposure to IFN-γ resulted in downregulation of the stem cell marker Lgr5. Only IFN-γ exposure resulted in increased production of caspase 3 and caspase 8. Exposure to either IFN-γ or IL1β resulted in suppressed cell proliferation. The pro-inflammatory cytokines caused reduced tight junction protein expression and compromised membrane integrity. These findings are important to understanding IEC response to different inflammatory stimuli and to broadening knowledge of gut physiology. Supported by ORIP (K01OD030515, R21OD031903).