Periostin in Inflammatory Bowel Disease (IBD) development and synergistic effects mediated via CCL5

Abstract

The incidence of IBD is rising all over the world and is affecting 1 in 4000 people in Europe and 1 in 16.000 in Asia. [1] Welldocumented, reliable numbers for Kazakhstan are currently not available but observations from local physicians (personal communication) suggest that numbers might be significantly higher than suggested by the literature. The matricellular protein Periostin has recently been shown to be involved in IBD [2] (and our own unpublished data). In a chemically induced murine model (dextrane sulfate sodium DSS) it mediates intestinal inflammation through the activation of NF-κB signaling, which suggests that periostin is a potential therapeutic target for inflammatory bowel disease [2]. CCL5, also know as RANTES, is a chemokine shown to be interacting with the G protein-coupled receptors CCR1, CCR3 and CCR5 [3]. In a recent study it could be shown that CCR5 expression correlates with the infiltration of inflammatory cells into the lamina propria of IBD patients [4]. Periostin is a matricellular protein originally isolated from osteoblasts and found to be preferentially expressed in the periosteum [5, 6]. Periostin contains an N-terminal secretory signal peptide, followed by a cysteine-rich domain, four internal homologous repeats, and a C-terminal hydrophilic domain. The four internal repeats exhibit homology to the axon guidance protein fasciclin I that is involved in the development of nervous system in invertebrates and were thus named fasciclin domains.