The absence of periostin and treatment with the CCR5 antagonist maraviroc significantly reduced the recruitment of CCR5-expressing cells and ameliorated weight loss in murine models of chemically induced colitis.
Targeted modulation of periostin and CCR5 signaling systems synergistically ameliorates inflammation in murine models of inflammatory bowel disease.
p-value: p=<0.001
Inflammatory bowel disease (IBD), comprising mainly Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract. In recent years, a wealth of data has been accumulated demonstrating the complex interplay of many different factors in the pathogenesis of IBD. Among these are factors impacting the epithelial barrier function, including vessel and extracellular matrix (ECM) formation, the gut microbiome (e.g., bacterial antigens), and, most importantly, the production of cytokines (pro- and anti-inflammatory) directly shaping the immune response. Patients failing to resolve the acute intestinal inflammation develop chronic inflammation. It has been shown that the expression of the matricellular protein periostin is enhanced during IBD and is one of the drivers of this disease. The C-C chemokine receptor 5 (CCR5) is engaged by the chemotactic mediators CCL3/MIP-1α, CCL4/MIP-1β, and CCL5/RANTES. CCR5 blockade has been reported to ameliorate inflammation in a murine IBD model. Thus, both periostin and CCR5 are involved in the development of IBD. In this study, we investigated the potential crosstalk between the two signaling systems and tested a highly potent CCL5 derivative acting as a CCR5 antagonist in a murine model of IBD. We observed that the absence of periostin influences the CCR5-expressing cell population of the gut. Our data further support the notion that targeted modulation of the periostin and CCR5 signaling systems bears therapeutic potential for IBD.
Mukanova et al. (Thu,) conducted a other in Inflammatory bowel disease (chemically induced colitis). Periostin deficiency and CCR5 antagonists (Maraviroc, CCL5 5p12 5m) vs. Wild-type mice / untreated mice was evaluated on Number of CCR5-expressing cells in the colon/intestine (p=<0.001). The absence of periostin and treatment with the CCR5 antagonist maraviroc significantly reduced the recruitment of CCR5-expressing cells and ameliorated weight loss in murine models of chemically induced colitis.
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