Researchers at the University of Padova in Italy discovered that a high expression of a small RNA molecule known as microRNA-155 leads to the inflammatory phenotype typically seen in patients with inflammatory bowel disease (IBD). The study was published in the journal Experimental & Molecular Medicine and is entitled “MiR-155 modulates the inflammatory phenotype of intestinal myofibroblasts by targeting SOCS1 in ulcerative colitis.”

IBD is a chronic, idiopathic inflammatory condition of the digestive tract that primarily comprises ulcerative colitis and Crohn’s disease. Patients with IBD can experience abdominal pain, vomiting, rectal bleeding, diarrhea, internal cramps in the pelvis region, fatigue and weight loss. It is unclear what triggers IBD, but the disorder is known to be associated with an immunological deregulation.

Evidence has suggested that intestinal myofibroblast (IMF) cells are involved in the inflammation process seen in the intestinal mucosa. In IBD patients, IMFs suffer a phenotype alteration that leads to tissue destruction, activation of immune cells and mucosal damage. Patients with IBD have also been reported to have abnormal levels of the microRNA (miR)-155. MicroRNAs are small non-coding RNA molecules that play critical roles in the regulation of gene expression. The miR-155 is known to be involved in inflammation and immune responses, although its role in IBD physiopathology is poorly elucidated.

In the study, researchers assessed the role of miR-155 and its relation to the IMF inflammatory phenotype. IMFs were collected from colonic biopsies of patients with ulcerative colitis and Crohn’s disease, and also from healthy controls. The levels of miR-155 in the different IMFs were determined at baseline and after exposure to pro-inflammatory molecules such as TNF-alpha, interleukin-1 beta and lipopolysaccharide (LPS).

Researchers found that miR-155 is significantly upregulated in IMFs from patients with ulcerative colitis but not in IMFs from healthy individuals or patients with Crohn’s disease. miR-155 expression in IMFs was found to be induced by pro-inflammatory molecules, like TNF-alpha and LPS. The team found that miR-155 overexpression in IMFs mimics the inflammatory phenotype seen in IMFs from ulcerative colitis patients, while miR-155 depletion amends the IMFs pro-inflammatory phenotype. Researchers also found that miR-155 directly targets a molecule called suppressor of cytokine signaling 1 (SOCS1), a potent molecular switch which is known to be significantly downregulated in IMFs from ulcerative colitis patients.

The team concluded that in patients with ulcerative colitis, inflammatory mediators induce the overexpression of miR-155 in IMFs, which in turn block SOCS1 expression leading to an IMF inflammatory phenotype. The team believes that their findings may lead to potential new anti-inflammatory therapies.