Annexin A1 Expression Capacity as a Determinant for Disease Severity in Crohn's Disease.

INTRODUCTION: Crohn's disease (CD) is characterized by relapsing intestinal inflammation. The anti-inflammatory protein annexin A1 (ANXA1) has been linked to inflammatory processes in the gut. OBJECTIVE: To examine ANXA1 expression patterns in the inflamed intestine of patients with CD and associate ANXA1 expression capacity with disease characteristics. METHODS: Surgical specimens of patients with CD operated between 2003 and 2015 were examined. Immunohistochemistry and immunofluorescence were performed to delineate ANXA1 expression. Those with pronounced ANXA1 expression were included in further analysis by qPCR. ANXA1 mRNA expression ratio of the inflamed to non-inflamed tissue was determined and defined as expression capacity of the tissue. Depending on their expression capacity, patients were divided into 2 groups (ANXA1-low vs. ANXA1-high), which were associated with clinical characteristics. RESULTS: Immunohistochemical ANXA1 expression was localized in inflamed regions of the intestine. In immunofluorescence, ANXA1 costained with myeloperoxidase as neutrophil marker, CD4 and CD8 as T cell marker but not CD20 as B cell marker or CD68 as macrophage marker. In qPCR, ANXA1 mRNA expression was upregulated by 20-fold in inflamed to noninflamed tissues. Patients with higher intrinsic ANXA1 expression capacity had significantly less severity of inflammation. Furthermore, the ANXA1-high group had significantly more locally restricted disease (p = 0.0070), more stricturating disease (p = 0.0037), and was less frequently treated by preoperative steroid therapy (p = 0.030). CONCLUSIONS: ANXA1 expression was strongly associated with intestinal inflammation and expressed in T cells and neutrophils of the CD tissues. Patients with higher intrinsic ANXA1 expression capacity of the inflamed tissue presented milder inflammatory changes and indolent clinical course.

Granin-derived peptides.

The granin family comprises altogether 7 different proteins originating from the diffuse neuroendocrine system and elements of the central and peripheral nervous systems. The family is dominated by three uniquely acidic members, namely chromogranin A (CgA), chromogranin B (CgB) and secretogranin II (SgII). Since the late 1980s it has become evident that these proteins are proteolytically processed, intragranularly and/or extracellularly into a range of biologically active peptides; a number of them with regulatory properties of physiological and/or pathophysiological significance. The aim of this comprehensive overview is to provide an up-to-date insight into the distribution and properties of the well established granin-derived peptides and their putative roles in homeostatic regulations. Hence, focus is directed to peptides derived from the three main granins, e.g. to the chromogranin A derived vasostatins, betagranins, pancreastatin and catestatins, the chromogranin B-derived secretolytin and the secretogranin II-derived secretoneurin (SN). In addition, the distribution and properties of the chromogranin A-derived peptides prochromacin, chromofungin, WE14, parastatin, GE-25 and serpinins, the CgB-peptide PE-11 and the SgII-peptides EM66 and manserin will also be commented on. Finally, the opposing effects of the CgA-derived vasostatin-I and catestatin and the SgII-derived peptide SN on the integrity of the vasculature, myocardial contractility, angiogenesis in wound healing, inflammatory conditions and tumors will be discussed.