The 5-HT3 receptor antagonist tropisetron inhibits T cell activation by targeting the calcineurin pathway

Vega, Laureano de la; Muñóz, Eduardo; Calzado, Marco A.; Lieb, Klaus; Candelario‐Jalil, Eduardo; Gschaidmeir, Harald; Färber, L; Mueller, Wolfgang; Stratz, T; Fiebich, Bernd L.

doi:10.1016/j.bcp.2005.04.031

Cited by 82 publications

(44 citation statements)

References 38 publications

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“…Tropisetron, a 5-HT 3 receptor antagonist, has been reported to be involved in various cell immune responses [16, 17]. Previous studies indicated that tropisetron possesses antiphlogistic and anti-inflammatory effects, which was thought to be related to the inhibition of proinflammatory mediator release and reduction of oxidative stress [18–21].…”

Section: Introductionmentioning

confidence: 99%

Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways

Liu

Lee

Liao

et al. 2016

BioMed Research International

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Objectives. To investigate the protective effects of tropisetron on acetaminophen- (APAP-) induced liver injury in a mice model. Methods. C57BL/6 male mice were given tropisetron (0.3 to 10 mg/kg) 30 minutes before a hepatotoxic dose of acetaminophen (300 mg/kg) intraperitoneally. Twenty hours after APAP intoxication, sera alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activities, and liver histopathological changes were examined. The MAP kinases were also detected by western blotting. Results. Our results showed that tropisetron pretreatment significantly attenuated the acute elevations of the liver enzyme ALT level, hepatic MPO activity, and hepatocytes necrosis in a dose-dependent manner (0.3–10 mg/kg) in APAP-induced hepatotoxicity mice. Tropisetron (1 and 3 mg/kg) suppressed APAP-induced hepatic lipid peroxidation expression and alleviated GSH and SOD depletion. Administration of tropisetron also attenuated the phosphorylation of c-Jun-NH2-terminal protein kinase (JNK) and extracellular signal-regulated kinase (ERK) caused by APAP. Conclusion. Our data demonstrated that tropisetron's hepatoprotective effect was in part correlated with the antioxidant, which were mediated via JNK and ERK pathways on acetaminophen-induced liver injury in mice.

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Section: Introductionmentioning

confidence: 99%

Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways

Liu

Lee

Liao

et al. 2016

BioMed Research International

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“…Our unpublished data show that tropisetron inhibits calcineurin activity in cerebellar granule neurons that lack 5-HT3 receptors. This could explain the superiority of tropisetron, when compared with granisetron, in suppressing IL-2 production by Jurkat T-cells [97]. We conclude that in addition to 5-HT3 receptor blockade, mechanisms including calcineurin inhibition account for anti-inflammatory and immunomodulatory effects of tropisetron.…”

Section: (Reza Rahimian and Pedram Ghafourifar)mentioning

confidence: 94%

Research update for articles published in EJCI in 2009

Abed

Adlbrecht

Señarís

et al. 2011

European Journal of Clinical Investigation

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“…Furthermore, the anti-inflammatory effect has been shown to be mediated by the inhibition of p38 mitogenactivated protein kinase expression, independent of the 5-HT 3 receptors. 30) In contrast, serotonin stimulated prostaglandin E 2 production in macrophage-like synovial cells via activation of the 5-HT 2A and 5-HT 3 receptors. 11) Granisetron has been shown to attenuate the inflammatory responses, including inflammatory cytokine production, in carrageenan-induced air pouch models.…”

Section: Mechanisms Of the Anti-inflammatory Effects Of The 5-ht 3 Rementioning

confidence: 95%

“…Anti-inflammatory effects Pathways Reference Tropisetron LPS-activated TNF-α and IL-1 production in monocytes p38 MAP kinase Stratz et al 30) Tropisetron Ondansetron…”

Section: -Ht 3 Receptor Antagonistsmentioning

confidence: 99%

“…Lipopolysaccharide-stimulated production of TNF-α and IL-1 was inhibited by tropisetron and ondansetron in human monocytes. 7,30) Tropisetron and ondansetron can inhibit IL-2 expression and T-cell activation via suppression of the calcineurin pathway. 31) However, granisetron, an equipotent antagonist of 5-HT 3 receptors, along with ondansetron, failed to inhibit T-cell functions, suggesting that this action of tropisetron and ondansetron is independent of 5-HT 3 receptors.…”

Section: Mechanisms Of the Anti-inflammatory Effects Of The 5-ht 3 Rementioning

confidence: 99%

See 1 more Smart Citation

Role of Serotonin 5-HT<sub>3</sub> Receptors in Intestinal Inflammation

Kato

2013

Biological & Pharmaceutical Bulletin

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Serotonin (5-hydroxytryptamine; 5-HT), a well-characterized neurotransmitter in the central nervous system, plays a crucial role in regulating mood, body temperature, sleep, appetite, and metabolism. Serotonin is synthesized in the serotonergic neuron of the central nervous system; however, approximately 90% of serotonin is synthesized and localized in the gastrointestinal (GI) tract, especially in the enterochromaffin (EC) cells. In the GI tract, serotonin mediates control over a variety of physiological functions such as contraction/relaxation of smooth muscle, and peristaltic and secretory reflexes, directly or indirectly through intrinsic primary afferent neurons. The receptors mediating the action of serotonin are mainly classified into 7 major groups known as the 5-HT1 to 5-HT7 receptors. The 5-HT3 receptor is distinguished from among the other 5-HT receptor subtypes because it is only a ligand-gated ion channel, whereas the other subtypes serve as G protein-coupled receptors. The 5-HT3 receptor, which is generally considered to be localized in the central and peripheral nervous systems, is involved in processes associated with emotion, cognition, memory, pain perception, and GI functions including secretion and motility. Recently, an increasing number of findings have provided evidence of the important role of the 5-HT3 receptor in the regulation of inflammatory and immune responses. In fact, several 5-HT3 receptor antagonists have been reported to ameliorate intestinal inflammation. Therefore, this review focuses on the role of 5-HT3 receptors in the pathogenesis of intestinal inflammation.

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The 5-HT3 receptor antagonist tropisetron inhibits T cell activation by targeting the calcineurin pathway

Cited by 82 publications

References 38 publications

Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways

Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways

Research update for articles published in EJCI in 2009

Role of Serotonin 5-HT<sub>3</sub> Receptors in Intestinal Inflammation

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