Abstract
Interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal (GI) tract and loss of ICC is associated with many GI motility disorders. Previous studies have shown that ICC have the capacity to regenerate or restore, and several growth factors are critical to their growth, maintenance or regeneration. The present study aimed to investigate the roles of interleukin-9 (IL-9) in the growth, maintenance and pacemaker functions of cultured ICC. Here, we report that IL-9 promotes proliferation of ICC, and culturing ICC with IL-9 enhances cholecystokinin-8-induced Ca2+ transients, which is probably caused by facilitating maintenance of ICC functions under culture condition. We also show co-localizations of cholecystokinin-1 receptor and IL-9 receptor with c-kit by double-immunohistochemical labeling. In conclusion, IL-9 can promote ICC growth and help maintain ICC functions; IL-9 probably performs its functions via IL-9 receptors on ICC.
Highlights
INTERLEUKIN-9 (IL-9), which is dependent upon Type 2 helper T cells, is a multifunctional cytokine that functions as either a positive or a negative regulator of immune responses
myosin heavy chain (MyHC) was observed but did not increase after sorting. (K) Immunohistochemical staining of cultured Interstitial cells of Cajal (ICC) using an antibody against ANO1; nuclei were stained with DAPI; negative control were treated in the same way but omitted the primary antibody. doi:10.1371/journal.pone.0095898.g001
It has been well documented that ICC play critical roles in GI motility and the loss of ICC is associated with many GI motility disorders
Summary
INTERLEUKIN-9 (IL-9), which is dependent upon Type 2 helper T cells, is a multifunctional cytokine that functions as either a positive or a negative regulator of immune responses. It is widely accepted that SCF, insulin-like growth factor-I (IGF-1) and insulin are critical to the development and functional maintenance of ICC [11,12,13] In addition to these growth factors, research from Dr Huizinga has revealed that IL-9 has a proliferative effect on ICC inside tissue explants and mast cells make membrane-to-membrane contact with injured ICC and exhibit piecemeal degranulation at the ultrastructural level [14,15]. This data suggested that IL-9 secreted by mast cells may promote growth and repair of ICC, indicating the possibility that other kinds of cell factors may enhance ICC proliferation and restoration in addition to growth factors. We observed the co-localizations of IL-9 receptor (IL-9R) and CCK1 receptor (CCK1R) with c-kit immunoreactivities in murine gastric antral tissues
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