Activation of protease-activated receptor 4 of mast cells could downregulate proinflammatory cytokines in irritable bowel syndrome

We read with interest the article by Wouters et al1 on mast cells (MCs) that dominate the mucosal inflammatory infiltrate in the intestine of functional GI disorders (FGIDs). Protease-activated receptor 4 (PAR4) is extensively expressed in MCs in allergic inflammation2 and may mediate an antinociceptive effect in gut visceral hyperalgesia.3 We wish to report the potential influence of PAR4 activation on the production of cytokines from MCs that might regulate sensitisation and subsequent heightened pain behaviour in FGIDs.4 5

Immunoreactivity for tryptase and PAR4 was analysed in the colonic mucosa of 21 patients with IBS with diarrhoea (IBS-D) and 16 healthy controls (figure 1A, B). Numbers of MCs were obtained by counting tryptase-immunoreactive cells. There were substantial increases in the numbers of both tryptase and PAR4-positive cells seen in IBS-D colonic mucosa compared with those in healthy...