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Activation of protease-activated receptor 4 of mast cells could downregulate proinflammatory cytokines in irritable bowel syndrome
  1. Shuhong An1,
  2. Guofang Zong2,
  3. Zhaojin Wang1,
  4. Juan Shi1,
  5. Hui Du3,
  6. Jiangong Hu2
  1. 1Department of Human Anatomy, Taishan Medical University, Taian, China
  2. 2Department of Gastroenterology, Affiliated Hospital of Taishan Medical University, Taian, China
  3. 3Department of Histology and Embryology, Taishan Medical University, Taian, China
  1. Correspondence to Dr Zhaojin Wang, Department of Human Anatomy, Taishan Medical University, 2 Ying Sheng Dong Lu, Taian 271000, China; zjwang{at}

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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 controls. Double labelling showed that PAR4 is highly expressed in tryptase-staining MCs in the colon of patients with IBS-D.

Figure 1

Immunohistochemical staining for tryptase (mast cells (MCs)) and protease-activated receptor 4 (PAR4) in colon sections of patients with IBS with diarrhoea (IBS-D), and the effect of PAR4 on interleukin (IL)-1β expression in bone marrow MCs (BMMCs). (A) Representative immunostaining for tryptase and PAR4 is shown. Colonic sections were incubated with antibodies against tryptase (Abcam) and PAR4 (Alomone Labs), and counterstained with toluidine blue. Scale bar represents 100 μm. (B) Graph showing the …

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  • Contributors ZW, SA and JH designed the overall project. GZ and JH were responsible for acquisition of data. SA, JS and HD performed in vitro experiments. ZW, SA and GZ were responsible for the analysis and interpretation of the data, and drafted the manuscript. All authors revised and approved the final manuscript.

  • Funding The study was supported by National Natural Science Foundation of China (No. 81371234) and Natural Science Foundation of Shandong Province, China (ZR2013HM032).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The Ethics Committee of the Taishan Medical University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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