J Neurogastroenterol Motil  https://doi.org/10.5056/jnm19099
Expression of Neurotrophic Factors, Tight Junction Proteins, and Cytokines According to Irritable Bowel Syndrome Subtype and Sex
Ju Yup Lee1, 2 , Nayoung Kim1, 3* , Ji Hyun Park3, Ryoung Hee Nam1, Sun Min Lee1, Chin-Hee Song1, Geun Kim1, Hee Young Na4, Yoon Jin Choi1, Jin Joo Kim5, Dong Ho Lee1, 3
1Department of Internal Medicine, Seoul National University Bundang Hospital, 2Department of Internal Medicine, Keimyung University School of Medicine, 3Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 4Department of Pathology, Seoul National University Bundang Hospital, 5Department of Internal Medicine, Gyeongsang National University Changwon Hospital
Correspondence to: Nayoung Kim, MD, PhD
Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam, Gyeonggi-do 13620, Korea
Tel: +82-31-787-7008, Fax: +82-31-787-4051, E-mail: nayoungkim49@empas.com
ORCID ID: Ju Yup Lee: 0000-0003-0021-5354/Nayoung Kim: 0000-0002-9397-0406
Received: May 8, 2019; Revised: August 26, 2019; Accepted: September 27, 2019; Published online: October 18, 2019.
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

Abstract
Background/Aims
Emerging evidence shows that the mechanism of irritable bowel syndrome (IBS) is associated with neurotrophic factors and tight junction proteins (TJPs) It is known that there are sex differences in the pathophysiology of IBS. The aim of the present study is to determine expression levels of neurotrophic factors, TJPs, and cytokines according to IBS subtype and sex.
Methods
From 59 IBS (33 IBS-constipation, 21 IBS-diarrhea, and 5 IBS-mixed) and 36 control patients, colonic mucosa mRNA expression levels of transient receptor potential vanilloid-1 (TRPV1), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), and various TJPs were assessed by real-time polymerase chain reaction. Western blot was performed to determine levels of zonular occludens-1 (ZO-1). Serum levels of cytokines were measured by enzyme-linked immunosorbent assay.
Results
TRPV1, GDNF, and NGF mRNA levels were significantly increased in those with IBS-constipation compared to those in controls (all P < 0.05). However, they showed no significant difference between those with IBS-diarrhea and controls. Expression level of TRPV1 correlated with that of GDNF (r = 0.741, P < 0.001) and NGF (r = 0.935, P < 0.001). ZO-1 RNA expression levels were lower (P = 0.021) in female IBS-diarrhea than those in controls, although they showed no significant differences between male IBS-diarrhea and controls. Serum IL-1β levels in female IBS were significantly higher than those of male IBS, especially in IBS-constipation (P < 0.001).
Conclusion
Our results suggest that neurotrophic factors and IL-1β are closely related to IBS-constipation and that decrease of ZO-1 is an important factor in female with IBS-diarrhea.
Keywords: Cytokines; Irritable bowel syndrome; Sex; Subtype; Tight junctions


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