Eotaxins induce the trafficking of eosinophils to the sites of
inflammation via
CC chemokine receptor 3 (CCR3). In this study, we investigated
eotaxin-3/
CC chemokine ligand 26 (CCL26) expression in the inflamed mucosa of patients with
inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for
eotaxin-3 expression in human colonic myofibroblasts. Eotaxin-3 mRNA and
protein expression was evaluated by real time-polymerase chain reaction (PCR) and
enzyme-linked
immunosorbent assay (ELISA), respectively. Eotaxin-3 mRNA expression was elevated significantly in the active lesions of
ulcerative colitis (UC) patients. Significant elevations were also observed in the active lesions of
Crohn's disease (CD) patients, but this was significantly lower than that detected in the active UC lesions. There were no significant increases in the inactive lesions of UC or CD patients. Colonic myofibroblasts were identified as a major source of
eotaxin-3 in the colonic mucosa, and
interleukin (IL)-4 and
IL-13 enhanced eotaxin-3 mRNA and
protein expression significantly in these cells. There was a significant positive correlation between mucosal
eotaxin-3 and IL-4 mRNA expression in the active lesions of IBD patients. The IL-4- and IL-13-induced eotaxin-3 mRNA expression was regulated by the signal transducer and activator of transcription-6 (STAT-6) and suppressor of
cytokine signalling (SOCS)1-mediated pathways.
Interferon (IFN)-γ acts as a negative regulator on the IL-4- and IL-13-induced
eotaxin-3 expression via STAT-1 activation.
Eotaxin-3 expression was elevated specifically in the active lesions of IBD, in particular UC.
Eotaxin-3 derived from colonic myofibroblasts may play an important role in the pathophysiology of UC.