Original Article

Digestive Diseases and Sciences

, Volume 55, Issue 10, pp 2922-2928

Subjects with Diarrhea-Predominant IBS Have Increased Rectal Permeability Responsive to Tryptase

  • Jae Woong LeeAffiliated withDepartment of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
  • , Jung Ho ParkAffiliated withDepartment of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine Email author 
  • , Dong I. L. ParkAffiliated withDepartment of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
  • , Jung-Hwan ParkAffiliated withDepartment of BioNano Technology and Gaehon BioNano Research Institute, Kyungwon University
  • , Hong Joo KimAffiliated withDepartment of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
  • , Yong Kyun ChoAffiliated withDepartment of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
  • , Chong I. L. SohnAffiliated withDepartment of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
  • , Woo Kyu JeonAffiliated withDepartment of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
  • , Byung Ik KimAffiliated withDepartment of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine

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Abstract

Background and Aims

Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) appear to have increased intestinal permeability; it has been suggested that activation of protease-activated receptor-2 (PAR-2) receptors is responsible for this alteration. The aims of this study are to evaluate (1) if rectal (large bowel) permeability is increased in IBS-D and (2) if tryptase plays a critical role in the altered permeability.

Methods

Rectal biopsies from 20 patients with IBS-D and 30 subjects without the condition (normal controls) were assessed for macromolecular permeability using horseradish peroxidase in Ussing chambers in the basal state and after addition of drugs to the basolateral side. Reverse-transcription polymerase chain reaction (RT-PCR) was performed using colonic biopsy tissues from patients with IBS-D and normal subjects.

Results

When tryptase was added to the basolateral (not mucosal) side of normal rectal biopsy tissues, permeability appeared to be proportional to the increase in tryptase concentration (P < 0.05) and was abolished by the addition of tryptase inhibitor (100 μM nafamostat; 1.568 ± 0.874 ng/2 h/mm2 to 0.766 ± 0.661 ng/2 h/mm2, n = 14, respectively, P < 0.01). Intestinal permeability in patients with IBS-D was significantly increased compared with controls (0.848 ± 0.0.600 ng/2 h/mm2, n = 21, P < 0.01). Nafamostat significantly reduced the enhanced permeability in IBS-D (0.934 ± 0.589 ng/2 h/mm2 to 0.247 ± 0.263 ng/2 h/mm2, n = 14, respectively, P < 0.05). Transcription levels of PAR2 measured by RT-PCR did not differ between IBS-D and normal subjects.

Conclusion

Tryptase seems to play an important role in the control of human colonic mucosal permeability, and enhanced tryptase activity was responsible for the increased permeability of rectal mucosa in IBS patients.

Keywords

Irritable bowel syndrome Tryptase PAR-2