Eotaxin-3 (CCL26) Expression in Human Pancreatic Myofibroblasts.

OBJECTIVES

Eosinophil infiltration is a histological feature of autoimmune pancreatitis (AIP). However, little is known about the mechanisms underlying eosinophilic infiltration. In this study, we aimed to investigate the expression of the eosinophil chemotactic protein, eotaxin-3, in human pancreatic myofibroblasts.

METHODS

Enzyme-linked immunosorbent assays and quantitative polymerase chain reactions were used to quantify eotaxin-3 protein and messenger RNA levels, respectively.

RESULTS

Eotaxin-3 expression was induced by T helper type 2 cytokines, interleukin-4 (IL-4) and IL-13, in time- and dose-dependent manners. Both IL-4 and IL-13 induced the rapid phosphorylation of STAT6 (signal transducer and activator of transcription 6), and STAT6-specific small interfering RNA significantly blocked IL-4- and IL-13-induced eotaxin-3 expression, indicating involvement of STAT6 signaling pathways in eotaxin-3 induction. In contrast, SOCS (suppressor of cytokine signaling) protein-specific small interfering RNA experiments suggested that the SOCS family proteins are negative regulators of IL-4- and IL-13-induced eotaxin-3 expression in pancreatic myofibroblasts. Interferon-γ significantly inhibited IL-4- and IL-13-induced eotaxin-3 expression, and this response was mediated by STAT1 activation.

CONCLUSIONS

Pancreatic myofibroblasts may be a cellular source of eotaxin-3 in the pancreas. The T helper type 2 cytokines, IL-4 and IL-13, are critical factors for the induction of eotaxin-3 in the pancreas.