# PAR-2-induced colonic inflammation does not depend upon paracellular permeability and lymphocyte infiltration

Nicolas Cenac, Rafael Garcia Villar, Laurent Ferrier, Jean Fioramonti, Lionel Bueno

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Nicolas Cenac, Rafael Garcia Villar, Laurent Ferrier, Jean Fioramonti, Lionel Bueno. PAR-2-induced colonic inflammation does not depend upon paracellular permeability and lymphocyte infiltration. 10th United European Gastroenterology Week, Oct 2002, Genève, Switzerland. 2002, Gut 51 (4 Suppl. 3). hal-01600599

HAL Id: hal-01600599

https://hal.science/hal-01600599

Submitted on 4 Jun 2020

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PAR-2-induced colonic inflammation and does not depend upon paracellular permeability and lymphocyte infiltration

N Cenac, R Garcia-Villar, L Ferrier, J Fioramonti, L Bueno

Activation of colonic PAR-2 receptor provokes colonic inflammation and increases mucosal paracellular permeability in mice. The mechanism of inflammation is under debate and could be a consequence of tight junction opening with passage of exogenous pathogens into the lamina propria

**Methods** : The present study aimed to further characterise PAR-2-induced effects. To investigate: (i) a dose-effect relationship between the peptide agonist (SLIGRL) concentration and paracellular permeability, four groups received an intracolonic administration of SLIGRL at the dose of 5, 10 or 100 µg/mouse; (ii) a possible relationship between paracellular permeability and mucosal inflammation, four groups received the MLCK inhibitor ML-7 (2mg/kg, i.p.) or vehicle and SLIGRL (100 µg/mice) or vehicle; (iii) a possible cause and effect relationship between TCD4+ cells and paracellular permeability, two groups of SCID mice received SLIGRL (100 µg/mice) or vehicle. For all groups, colonic permeability was assessed with an intracolonic infusion of 51Cr-EDTA for 4h after SLIGRL or vehicle administration, followed by the determination of 51Cr-EDTA radioactivity in blood (cpm/ml). Pieces of colon were taken for myeloperoxidase assay (MPO; U/g of protein) and histologic examination (microscopic damage score, MDS). Values are expressed as mean ± SEM for each group.

**Results** : (i) At 10 and 100 µg SLIGRL increased paracellular permeability (903 ± 102 and 1721 ± 241 vs. 307 ± 41, p<0.01), MPO activity (239 ± 14 and 638 ± 198 vs. 49 ± 5, p<0.05) and MDS (4.8 ± 0.1 and 5.8 ± 0.60 vs. 0.8 ± 0.06, p<0.01). In contrast, at 5 µg SLIGRL increased paracellular permeability (307 ± 41 vs. 754 ± 78, p<0.05) but did not affect MPO nor MDS. (ii) ML-7 prevented SLIGRL-induced increase in permeability (119.3 ± 56.39 vs. 675.6 ± 94.5, p<0.01) but did not prevent MPO increase nor MDS increase. (iii) In SCID mice SLIGRL increased paracellular permeability (1685 ± 257 vs. 939 ± 173, p<0.05), MPO activity (300 ± 78 vs. 44 ± 9, p<0.01) and MDS (5.8 ± 0.60 vs. 0.8 ± 0.06, p<0.001).

**Conclusion** : The SLIGRL-induced inflammation does not result from an increase of paracellular permeability linked to activation of MLCK and does not require the presence of mature lymphocytes. In addition, distinct pathways account for SLIGRL-induced inflammation and alterations of permeability observed for a non-inflammatory dose.
From: Richard Torriani <richard.torriani@mci-group.com>
To: "'ncenac@toulouse.inra.fr'" <ncenac@toulouse.inra.fr>
Subject: UEGW TRAVEL GRANT AWARD
Date: Tue, 2 Jul 2002 11:28:44 +0200
X-Mailer: Internet Mail Service (5.5.2655.55)

PLEASE DISREGARD THE TITLE OF THE PREVIOUS EMAIL, THIS EMAIL IS TO
CONFIRM TRAVEL GRANT AWARD

Mr Nicolas Cenac
Neuro-Gastroenterology & Nutrition
INRA
180 chem de Tournefeuille
31931 Toulouse
France

Geneva, 25

June 2002

10th United European Gastroenterology Week "UEGW 2002"
Geneva, Switzerland, 19-23 October 2002

Dear Doctor Nicolas Cenac

Thank you for having submitted an abstract for "UEGW 2002" to be held in
Geneva in October.

On behalf of the UEGW Scientific Programme Committee, we are very happy to
inform you that you have been selected to receive a TRAVEL GRANT OF EURO
1000 based upon the excellent quality of your abstract. This TRAVEL GRANT is
non-transferable and will only be awarded to Nicolas Cenac.

As you know, you MUST register for the congress. The UEGW Scientific Programme Committee is delighted to propose registration at the early registration rate of Euro 420. Please note, that in order to benefit from this rate, you must register before the 15th of July 2002. In addition, as registration for the congress is obligatory, your abstract and the associated travel grant will withdrawn if you have not registered before this date. Please contact us if you require further registration information or visit our website www.uegf.org/uegw2002 for registration.

The travel grants will only be awarded onsite at the UEGW Registration desk. It will NOT be possible to receive these funds in advance. The travel grant is non-transferrable and will only be provided to the named recipient upon presentation of this document, proof of identity, and proof of age (you must be under 35 years of age).

We look forward to seeing you in Geneva and remain at your convenience for
any further information you may require.

On behalf of the "UEGW 2002" Organising Committee, we remain

Sincerely yours,

MCI Congress

Richard Torriani
Project Manager