Differential Expression of IL-36 Family Members and IL-38 by Immune and Nonimmune Cells in Patients with Active Inflammatory Bowel Disease

Abstract

IL-1 family includes IL-38 (IL-1F10) and the subfamily of IL-36 and is the central mediators of inflammatory diseases, including pustular psoriasis, atopic dermatitis, rheumatoid arthritis, and gut inflammation. The purpose of the study was to evaluate on tissue of the patients with inflammatory bowel disease (IBD), the IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 gene and cell expression and its correlation with clinical activity. Patients and Methods. A cross-sectional and comparative study was performed. Seventy patients with IBD and 30 noninflamed non-IBD controls were enrolled. Gene expression was measured by RT-PCR. Protein expression was detected by double-staining immunohistochemistry. Results. The mRNA expression of IL-36 family members but not IL-38 was increased in colonic mucosa from patients with active ulcerative colitis versus Crohn's disease group and noninflammatory control group (P<0.05). However, only gene expression of IL-38 was increased in tissue from patients with inactive ulcerative colitis versus active disease and control group (P<0.005). Conversely, gene expression of IL-36Ra was significantly higher in colonic tissue from patients with active versus inactive ulcerative colitis and noninflamed control group (P<0.05). A differential protein overexpression of IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 by intestinal epithelial cells, macrophages, CD8+ T cells, and/or versus dendritic cells (pDCs) was found in patients with active inflammatory bowel disease compared with noninflamed controls. Conclusion. IL-38 and IL-36 family members' expression was increased by immune and nonimmune cells in patients with active inflammatory bowel disease. These cytokines and IL-36Ra might represent novel therapeutic targets in patients with gut inflammation.

Current perspectives on the interleukin‐1 family as targets for inflammatory disease

“…Similar to related IL‐1 family members, the role of IL‐36 in the gut is complex. While some studies have demonstrated that IL‐36 has a pro‐inflammatory role , other studies have described its role in promoting the resolution of intestinal inflammation . On the one hand, IL‐36 signalling facilitates neutrophil and inflammatory monocyte infiltration to intestinal tissues and can regulate the balance of pro‐inflammatory mucosal CD 4+ T cell subsets .…”

Gene Expression Profiling of Mediators Associated with the Inflammatory Pathways in the Intestinal Tissue from Patients with Ulcerative Colitis

“…The diagnosis of UC was done by the presence of the following criteria: a history of diarrhea or blood in stools and macroscopic appearance by endoscopy and biopsy compatible with UC [6][7][8][9][10].…”

“…The control group did not take any medication. All individuals underwent colonoscopy for taking colonic biopsies before signing the written informed consent [6][7][8][9][10].…”

“…In order to isolate high-quality RNA, the rectal biopsy was taken by colonoscopy and immediately submerged in 0.5 ml of RNA later stabilization solution (Ambion, Austin, TX, USA) for storage and stored at -80°C until used. Then, total RNA was isolated using High Pure RNA Tissue (Roche Diagnostics, Mannheim, Germany) [6,7].…”

Gene Expression Profiling of Inflammatory Cytokines in Esophageal Biopsies of Different Phenotypes of Gastroesophageal Reflux Disease: a cross-sectional study.

“…Two hundred nanograms of total RNA was reverse transcribed into cDNA with random hexamer primers (Roche Diagnostics, Mannheim, Germany). The methodology employed was based on the previous studies of gene expression [6][7][8] PCR ampli cation was carried out with 20 ng of cDNA, 200 nM forward, reverse primer, and Taqman Master Mix (Roche Diagnostics, Mannheim, Germany Roche Diagnostics, Mannheim, Germany) in a nal volume of 10 µl (Table 1). PCR reactions were run in a Light Cycler 480 (Roche Diagnostics, Mannheim, Germany) for 45 cycles, each cycle consists in denaturation for 15 seconds at 95°, primer annealing for 15 seconds at 55°C, and extension for 30 seconds at 72°C and cooling 30 seconds at 40°C.…”