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Lessons on the Sigma-1 Receptor in TNBS-Induced Rat Colitis: Modulation of the UCHL-1, IL-6 Pathway.


ABSTRACT: Inflammatory Bowel Disease (IBD) is an autoimmune ailment of the gastrointestinal (GI) tract, which is characterized by enhanced activation of proinflammatory cytokines. It is suggested that the sigma-1 receptor (?1R) confers anti-inflammatory effects. As the exact pathogenesis of IBD is still unknown and treatment options are limited, we aimed to investigate the effects of ?1R in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis. To this end, male Wistar-Harlan rats were used to model colitic inflammation through the administration of TNBS. To investigate the effects of ?1R, Fluvoxamine (FLV, ?1R agonist) and BD1063 (?1R antagonist) were applied via intracolonic administration to the animals once a day for three days. Our radioligand binding studies indicated the existence of ?1Rs as [3H](+)-pentazocine binding sites, and FLV treatment increased the reduced ?1R maximum binding capacity in TNBS-induced colitis. Furthermore, FLV significantly attenuated the colonic damage, the effect of which was abolished by the administration of BD1063. Additionally, FLV potentially increased the expression of ubiquitin C-terminal hydrolase ligase-1 (UCHL-1) and the levels of endothelial nitric oxide synthase (eNOS), and decreased the levels of interleukin-6 (IL-6) and inducible NOS (iNOS) expression. In summary, our study offers evidence for the anti-inflammatory potential of FLV and ?1R in experimental colitis, and our results present a promising approach to the development of new ?1R-targeted treatment options against IBD.

SUBMITTER: Almasi N 

PROVIDER: S-EPMC7312485 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Lessons on the Sigma-1 Receptor in TNBS-Induced Rat Colitis: Modulation of the UCHL-1, IL-6 Pathway.

Almási Nikoletta N   Török Szilvia S   Dvorácskó Szabolcs S   Tömböly Csaba C   Csonka Ákos Á   Baráth Zoltán Z   Murlasits Zsolt Z   Valkusz Zsuzsanna Z   Pósa Anikó A   Varga Csaba C   Kupai Krisztina K  

International journal of molecular sciences 20200605 11


Inflammatory Bowel Disease (IBD) is an autoimmune ailment of the gastrointestinal (GI) tract, which is characterized by enhanced activation of proinflammatory cytokines. It is suggested that the sigma-1 receptor (σ1R) confers anti-inflammatory effects. As the exact pathogenesis of IBD is still unknown and treatment options are limited, we aimed to investigate the effects of σ1R in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis. To this end, male Wistar-Harlan rats were us  ...[more]

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2007-12-10 | GSE5864 | GEO