Substance P and calcitonin gene related peptide induce TGF-alpha expression in epithelial cells via mast cells and fibroblasts

Abstract

Objective/background: Signals for the expression of EGF, TGFalpha and related proteins are largely unknown. Having shown earlier, that activation of the afferent sensory nervous system by capsaicin induced epithelial cell proliferation and TGFalpha expression in vivo the aim of this study was to demonstrate, that neurotransmitters of the afferent sensory nervous system induce TGFalpha expression via mast cells and fibroblasts.

Results: A significant increase in TGFalpha-mRNA and protein expression was detected in epithelial cells exposed to supernatants of CGRP-stimulated mast cells and SP-stimulated fibroblasts. Epithelial cell proliferation was only detected in epithelial cells exposed to supernatants of CGRP-stimulated mast cells but not in epithelial cells exposed to supernatants of SP-stimulated fibroblasts. TGFbeta mRNA expression was increased in epithelial cells exposed to fibroblasts but not to mast cells. No increase in EGF-receptor expression was detected in epithelial cells exposed to either fibroblast or mast cell supernatants.

Conclusion: Neurotransmitters of the afferent sensory nervous system induce TGFalpha expression in epithelial cells mediated by mast cells and fibroblasts. Release of CGRP and SP from neuroeffector junctions is an important signal for the TGFalpha expression after mucosal injury. Mucosal expression of TGFalpha may contribute to the protective effects of the sensory nervous system after mucosal injury.