Expression of Neurotrophic Factors, Tight Junction Proteins, and Cytokines According to the Irritable Bowel Syndrome Subtype and Sex - PubMed (original) (raw)

Expression of Neurotrophic Factors, Tight Junction Proteins, and Cytokines According to the Irritable Bowel Syndrome Subtype and Sex

Ju Yup Lee et al. J Neurogastroenterol Motil. 2020.

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).

Conclusions: 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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Conflict of interest statement

Conflicts of interest: None.

Figures

Figure 1

Figure 1

Transient receptor potential vanilloid-1 (TRPV1), nerve growth factor (NGF), and glial derived neurotrophic factor (GDNF) mRNA expression levels in the colonic mucosa of irritable bowel syndrome (IBS) patients. (A–C) Significantly higher expression levels of TRPV1, NGF, and GDNF were observed in constipation type IBS (IBS-C) patients compared to controls. (D, E) There was a strong positive relationship between TRPV1 and NGF or GDNF (r = 0.935, P < 0.0001 for NGF; r = 0.741, P < 0.0001 for GDNF). IBS-D, diarrhea type irritable bowel syndrome; IBS-M, mixed type irritable bowel syndrome.

Figure 2

Figure 2

Zonula occludens-1 (ZO-1), occludin (OCLN), and claudin-1 (CLDN1) mRNA expression levels in the colonic mucosa of IBS patients according to IBS subtype and sex. (A) Female irritable bowel syndrome (IBS) patients showed significantly lower ZO-1 mRNA expression levels, especially in diarrhea type IBS (IBS-D) and mixed type IBS (IBS-M) than control females (P = 0.021). (B, C) OCLN and CLDN1 mRNA expression levels were similar among subtypes and sexes. IBS-C, constipation type irritable bowel syndrome.

Figure 3

Figure 3

Western blot analysis of zonula occludens-1 (ZO-1) mRNA expression level in each irritable bowel syndrome (IBS) subtype and sex. (A, B) ZO-1 mRNA expression levels in diarrhea type IBS (IBS-D) and mixed type IBS (IBS-M) patients were significantly lower than those of the control group. (C) Sex difference of ZO-1 mRNA expression in IBS-D compared with control (*P < 0.05). Con, control; C, constipation type; D, diarrhea type; M, mixed type; IBS-C, constipation type irritable bowel syndrome.

Figure 4

Figure 4

Serum levels of (A) interleukin-8 (IL-8), (B) tumor necrosis factor-α (TNF-α), and (C) IL-1β cytokines in irritable bowel syndrome (IBS) patients and controls according to IBS subtype and sex. (C) Serum IL-1β level was significantly higher in female IBS patients than that in male IBS patients, especially in constipation type IBS (IBS-C) (*P < 0.001). IBS-D, diarrhea type irritable bowel syndrome; IBS-M, mixed type irritable bowel syndrome.

References

    1. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130:1480–1491. doi: 10.1053/j.gastro.2005.11.061. -DOI -PubMed
    1. Oshima T, Miwa H. Gastrointestinal mucosal barrier function and diseases. J Gastroenterol. 2016;51:768–778. doi: 10.1007/s00535-016-1207-z. -DOI -PubMed
    1. Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10:712–721. e4. doi: 10.1016/j.cgh.2012.02.029. -DOI -PubMed
    1. Kim YS, Kim N. Sex and gender differences in irritable bowel syndrome. J Neurogastroenterol Motil. 2018;24:544–558. doi: 10.5056/jnm18082. -DOI -PMC -PubMed
    1. Houghton LA, Heitkemper M, Crowell M, et al. Age, gender and women’s health and the patient. Gastroenterology. 2016;150:1332–1343. e4. doi: 10.1053/j.gastro.2016.02.017. -DOI -PubMed

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