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*P<0.05 (Student’s t-test). C) Expression of junctional proteins in the apical region of Caco-2 monolayers compared to untreated controls

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Supplementary Figure 1. Representative photomicrographs showing each grade of staining for JAM-A protein. Bars=50 μm.

Grade 3

Grade 2 Grade 4

Grade 1

(2)

Supplementary Figure 2. Expression of junctional proteins (CLD-3, occludin, CLD-2, E-cadherin) in Caco-2 monolayers incubated with tryptase, T, (3 mU or 15 mU) for up to 24 hours. A) Blots show a representative of a minimum of two independent experiments. B) The results are expressed as a change relative to untreated controls.

The density of each individual band was compared with the corresponding control band and normalised against GAPDH by densitometry. *P<0.05 (Student’s t-test). C) Expression of junctional proteins in the apical region of Caco-2 monolayers compared to untreated controls. Bars=20 μm.

CLD-3 GAPDH

Occludin GAPDH

CLD-2 GAPDH

E-cadherin

GAPDH

0 1 2

E-cadherin (% control) 0 1 2

CLD-2 (% control) 0 1 2 3

Occludin (% control) 0 2 4

CLD-3 (% control)

Time (h) C 1 2 4 1 2 4 C 24 24

Time (h) C 1 2 4 1 2 4 C 24 24

Time (h) C 1 2 4 1 2 4 C 24 24

Time (h) C 1 2 4 1 2 4 C 24 24

*

* *

Control 3 mU T 1 h 15 mU T 1 h

3 mU T 2 h 3 mU T 4 h 15 mU T 2 h 15 mU T 4 h 15 mU T 24 h

3 mU T 24 h

Control

A) B)

3 mU T

Control 15 mU T

Control 15 mU tryptase 4 h

CLD-3 Occludin

Control 15 mU tryptase 4 h C)

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Supplementary Table 1. Expression of JAM-A in control group according to gender and age (years) of patients at the time of biopsy. The expression was assessed semiquantitatively using a 4-grade scale. A) Analysis of controls according to gender and age < 32 years (the average age of IBS) and ≥ 32 years and resultant JAM-A expression (grade). Data were analysed with Mann-Whitney U test. B) Data were analysed with Spearman correlation and J-T test.

Gender, median (range) Age at the time of biopsy (years)

Males (n=7) Females (n=5) 26±2.7 51.6±4.4

JAM-A 4 (3-4) 4 (1-4) 4 (3-4) 4 (1-4)

P=0.63 P=0.61

Age at the time of biopsy (years)

Spearman correl. J-T test

rs P P

JAM-A -0.33 0.3 0.275

A)

B)

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