Role of periostin in inflammatory bowel disease development and synergistic effects mediated by the CCL5–CCR5 axis

Abstract

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.

ITGB2 related to immune cell infiltration as a potential therapeutic target of inflammatory bowel disease using bioinformatics and functional research

“… 41 CCR5 is upregulated in IBD, 42 and CCR5 blockade ameliorates inflammation in mice with IBD. 43 However, the role of ITGB2 in the pathogenesis of IBD has not been studied.…”

Photodynamic Effects with 5-Aminolevulinic Acid on Cytokines and Exosomes in Human Peripheral Blood Mononuclear Cells from Patients with Crohn’s Disease

“…Eotaxin may play a role in a number of diseases including inflammatory bowel diseases such as CD [48]. Regulated upon activation normal T-cell expressed and presumably secreted (RANTES), also known as chemokine ligand 5 (CCL5), might be interesting in the treatment of inflammatory bowel disease (IBD) [49].…”