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Comparison of Cytokine and Efflux Transporter Expression in Pediatric Versus Adult-onset Ulcerative Colitis
Ana Savić Mlakar1, Iva Hojsak, Mladen Jergović
1*Center for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Croatia †Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Croatia ‡Department of Gastroenterology, Clinical Hospital "Dubrava," School of Medicine, University of Zagreb, Croatia §Department of Gastroenterology, Clinical Hospital Center "Sisters of Mercy," School of Medicine, University of Zagreb, Croatia ||Croatian Veterinary Institute, Zagreb, Croatia.
Insights
Pediatric ulcerative colitis (UC) shows distinct molecular patterns compared to adults, with higher inflammatory cytokine levels in children and altered efflux transporter expression. Increased IL-2 in remission suggests a role for regulatory T cells.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon.
- Pediatric UC often presents with greater severity than adult-onset disease.
- Understanding age-related molecular differences in UC is crucial for targeted therapies.
Purpose of the Study:
- To investigate differential gene expression of efflux transporters, cytokines, and SOCS molecules in pediatric versus adult UC patients.
- To identify molecular patterns associated with disease severity and remission across age groups.
- To explore potential age-specific mechanisms in UC pathogenesis.
Main Methods:
- Mucosal samples from the terminal ileum and colon of pediatric and adult UC patients (newly diagnosed and in remission) and healthy controls were analyzed.
- Messenger RNA (mRNA) expression levels of efflux transporters, cytokines (e.g., IL-6, IL-17A, IFN-γ, IL-1β, IL-2), and suppressor of cytokine signaling (SOCS) molecules were quantified.
- Expression patterns were compared between patient groups and controls, and correlated with disease activity.
Main Results:
- Inflamed colonic tissues showed elevated IL-6, IL-17A, and IFN-γ in newly diagnosed UC patients of both age groups, with higher levels in children.
- IL-1β was increased only in newly diagnosed pediatric UC patients.
- Multidrug resistance protein 1 (MDR1) expression was decreased in the colon of both adult and pediatric UC patients, inversely correlating with disease severity and inflammatory markers.
- IL-2 expression was upregulated in patients with UC in remission.
Conclusions:
- Efflux transporter expression profiles differ between pediatric and adult UC, with the exception of MDR1.
- UC is characterized by a dysregulated TH1 and TH17 cytokine response, more pronounced in children.
- Elevated IL-2 during remission suggests a potential protective role for regulatory T cells (Tregs) in UC recovery.
Objectives:
Ulcerative colitis (UC), a chronic inflammation of the colon, is often more severe in children than adults. Identification of altered expression of efflux transporters, cytokines, and suppressor of cytokine signaling (SOCS) molecules in pediatric versus adult patients could provide insight into the differential molecular patterns related to the age and disease pathology.
Methods:
Mucosal samples from terminal ileum and colon in pediatric (9 UC-New, 4 UC-Remission) and adult (9 UC-New, 8 UC-Remission) patients were compared with healthy subjects (15 children and 10 adults) for mRNA expressions of several efflux transporters, cytokines, and SOCS molecules.
Results:
The inflamed colon interleukin (IL)-6, IL-17A, and interferon-γ levels were elevated in UC-New subgroups but close to control values in UC-Remission. IL-1β expression was increased only in UC-New children. Interestingly, uninflamed ileum also showed increased IL-6 and IL-1β levels in UC-New subgroups. SOCS1/SOCS3 expression pattern followed a trend observed for inflammatory cytokines only in children. Both children and adults had decreased multidrug resistance protein 1 expression in colon, which inversely correlated with disease score, IL-6 and interferon-γ levels in UC-New children. IL-2 expression was upregulated in UC-Remission, compared with controls.
Conclusions:
Efflux transporter expression varies between UC children and adults except for decreased multidrug resistance protein 1. UC is characterized by a dysregulated TH1 and TH17 cytokine response irrespective of age at disease onset, with higher cytokine levels detected in children. Increased IL-2 levels in remission imply a protective role for regulatory T cells (Tregs).
