Anti-CCL25 polyclonal antibody

Introduction: Chronic rhinosinusitis (CRS) is a local inflammation of the nasal mucosa and sinus that persists for >12 weeks. As CC chemokine ligand (CCL) 19 expression is known to be elevated in CRS, and CCL 19, CCL21, and CCL25 share the same atypical chemokine receptor 4, so we focused on CCL21 and CCL25. Objectives: To investigate the expression of CCL21 and CCL25 in different types of CRS and their significance in CRS development. Methods: A total of 116 patients participated in the study, and uncinate process mucosa or nasal polyp (NP) specimens were collected during surgery. Western blotting and immunohistochemistry were performed to detect the expression of CCL21 and CCL25, respectively, in the nasal mucosa. Immunofluorescence was used to determine their cellular localization in NPs, whereas macrophage culture was used to determine their relationships with macrophages. Results: Immunohistochemistry revealed that the expressions of CCL21 and CCL25 were increased in NPs only. Western blotting revealed that these expressions were gradually increased in control, CRS without NP and CRS with NP groups and were positively correlated with disease severity. Furthermore, increased expressions of CCL21 and CCL25 in NPs were not related to eosinophil infiltration. Immunofluorescence results demonstrated colocalization of CCL25+ cells and CD68+ macrophages. CCL25 expression was increased in macrophage culture, especially in M1 macrophages, while CCL21 expression was not significantly associated with macrophages. Conclusions: CCL21 and CCL25 were significantly upregulated in NPs and positively correlated with disease severity. CCL25 upregulation was related to M1 macrophages.

CCR9 expressed on T lymphocytes mediates migration to the small intestine in response to a gradient of CCL25. CCL25-stimulated activation of alpha(4)beta(7) integrin promotes cell adherence to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed by vascular endothelial cells of the intestine, further mediating gut-specific homing. Inflammatory bowel disease is a chronic inflammatory condition that primarily affects the gastrointestinal tract and is characterized by leukocyte infiltration. Glucocorticoids (GCs) are widely used to treat inflammatory bowel disease but their effect on intestinal leukocyte homing is not well understood. We investigated the effect of GCs on the gut-specific chemokine receptor pair, CCR9 and CCL25. Using human peripheral blood-derived T lymphocytes enriched for CCR9 by cell sorting or culturing with all-trans retinoic acid, we measured chemotaxis, intracellular calcium flux, and alpha(4)beta(7)-mediated cell adhesion to plate-bound MAdCAM-1. Dexamethasone (DEX), a specific GC receptor agonist, significantly reduced CCR9-mediated chemotaxis and adhesion to MAdCAM-1 without affecting CCR9 surface expression. In contrast, in the same cells, DEX increased CXCR4 surface expression and CXCL12-mediated signaling and downstream functions. The effects of DEX on human primary T cells were reversed by the GC receptor antagonist mifepristone. These results demonstrate that GCs suppress CCR9-mediated chemotaxis, intracellular calcium flux, and alpha(4)beta(7)-mediated cell adhesion in vitro, and these effects could contribute to the efficacy of GCs in treating intestinal inflammation in vivo.