INTERLEUKIN (IL)-12 RECEPTOR β2 SUBUNIT EXPRESSION IS UP-REGULATED IN CROHN'S DISEASE

Abstract

81 Background. IL-12 modulates immune response in chronic colitis. IL-12 mediates its functions by binding to a membrane receptor, composed by at least two subunits: β1 and β2. IL-12 responsiveness correlates with IL-12Rβ2 content and studies in experimental models showed that IL-12Rβ2 is preferentially expressed by Th1 cells. Aim. To examine whether IL-12Rβ2 expression is up-regulated in Crohn's disease (CD). Specific aims were: a. to demonstrate transcripts for IL-12Rβ2 in CD tissue; b. to investigate whether transcripts for IL-12Rβ2 are differently expressed in early and late CD; to explore whether corticosteroid (CS) treatment may affect IL-12Rβ2 expression. Materials and methods. Eight paediatric (mean age: 8±3 yrs), with a recent onset of disease (< 1 year), and ten adult (mean age: 36±18 yrs) (disease established for at least 4 years) CD patients were enrolled. Four out of 8 paediatric and 4 of 10 adult CD patients were on corticosteroid treatment. All patients had an active disease at the time of study. Two biopsy specimens were taken from involved colonic areas during endoscopy. Controls included 5 adult and 2 paediatric patients with irritable bowel syndrome. Total RNA was extracted from freshly obtained biopsy specimens and retrotranscripted in cDNA. IL-12Rβ2 was tested by semiquantitative reverse transcription-PCR and level of expression assessed as a ratio of IL-12Rβ2/β-actin signal intensity. Results. Transcripts for IL-12Rβ2 were detected in all tested samples. When IL-12Rβ2 was examined in a semiquantitative manner, a more pronounced (p<0.05) expression was found in CD patients (0.6±0.3) in comparison to controls (0.3±0.1). No difference in IL-12Rβ2 mRNA accumulation was observed between paediatric and adult CD patients. In patients off CS treatment the amount of transcripts for IL-12Rβ2 was higher (p<0.05) than in patients on CS treatment. This was evident in either paediatric and adult patients (0.9±0.25 vs 0.32±0.2 and 0.95±0.3 vs 0.28±0.1, p<0.05, respectively). No difference was observed between CD patients on CS treatment and controls. Conclusion. IL-12Rβ2 is upregulated in CD, further supporting the concept that IL-12 is involved in modulating local immune response in CD.