Keywords

IEC-18; Necrotizing Enterocolitis; gp130; IL-27; inflammatory cytokines; ZO-1

Abstract

Necrotizing enterocolitis (NEC) is a multifactorial intestinal disease involving systemic inflammatory responses in preterm infants. It affects 1–10% of all newborns (NB) admitted to the neonatal intensive care unit and has an overall mortality rate ranging between 10% in mild disease to 100% in more severe cases, yet survivors still suffer life-long complications. The pathogenesis of necrotizing enterocolitis (NEC) involves multiple factors that lead to inflammation of the intestines and subsequent injury to the intestinal epithelial barrier. Maintenance of barrier integrity is due in part to tight junction proteins, such as zona occludens-1 (ZO-1) and occludin. Previous work has shown that cytokines belonging to the IL-12 family, namely IL-12 and IL-23, alter ZO-1 and cause barrier dysfunction in cellular and animal models. It is still unclear whether initial breakdown is mediated through IL-12 Receptor (R) or IL-23 Receptor (R). Newly described cytokines belonging to this family may also play a role in the recovery mechanism. In our study, we propose that recovery occurs when the EBI3 subunit from the anti-inflammatory cytokine, IL-27, binds to the gp130 receptor on intestinal epithelial cells, activating STAT3, later inhibiting NF-κB activation, and thus, reducing pro-inflammatory cytokine production and subsequent ZO-1 breakdown. Elucidating the inflammatory pathway and major cytokines involved contributes to the largely unknown etiology and pathogenesis of the disease, as well as serve as a basis for the development of a screening protocol.

Thesis Completion Year

2024

Thesis Completion Semester

Fall

Thesis Chair

Liedel, Jennifer

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Thesis Discipline

Molecular Microbiology

Language

English

Access Status

Campus Access

Length of Campus Access

5 years

Campus Location

Orlando (Main) Campus

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Rights Statement

In Copyright