Mast cell stabilizing effect of a geranyl acetophenone in dengue virus infection usingin vitromodel of DENV3-induced RBL-2H3 cells

Abstract

Mast cells (MCs), a type of immune effector cell, have recently become recognized for their ability to cause vascular leakage during dengue virus (DENV) infection. Although MC stabilizers have been reported to attenuate DENV induced infection in animal studies, there are limited in vitro studies on the use of MC stabilizers against DENV induced MC degranulation. 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA) has been reported to be a potential MC stabilizer by inhibiting IgE-mediated MC activation in both cellular and animal models. The present study aims to establish an in vitro model of DENV3-induced RBL-2H3 cells using ketotifen fumarate as a control drug, as well as to determine the effect of tHGA on the release of MC mediators upon DENV infection. Our results demonstrated that the optimal multiplicities of infection (MOI) were 0.4 × 10−2 and 0.8 × 10−2 focus forming units (FFU)/cell. Ketotifen fumarate was proven to attenuate DENV3-induced RBL-2H3 cells degranulation in this in vitro model. In contrast, tHGA was unable to attenuate the release of both β-hexosaminidase and tumor necrosis factor (TNF)-α. Nonetheless, our study has successfully established an in vitro model of DENV3-induced RBL-2H3 cells, which might be useful for the screening of potential MC stabilizers for anti-dengue therapies.

A Panel of Broad-Spectrum Antivirals in Topical Ophthalmic Medications from the Drug Repurposing Approach during and after the Coronavirus Disease 2019 Era

“…Surprisingly, several antihistamines, such as chlorcyclizine, chlorpheniramine, and diphenhydramine, have demonstrated antiviral action against hepatitis C virus (HCV), filoviruses (consisting of Ebola virus, Marburg virus, and Cuevavirus), and Influenza A virus infection [78][79][80]. Of note, ketotifen fumarate has proven to attenuate dengue virus infection [81]. Controversial results of antihistamines in antiviral effects appear to be associated with herpes simplex virus (HSV) infection [82].…”

Host immune response against DENV and ZIKV infections

“…This implicates the important role played by the virus in inducing release of mast cell mediators that reflects on the clinical symptoms of DENV disease observed. Many studies have been conducted with drugs targeting vasoactive mast cell mediators and suggest that this may be one mode of treatment in DENV disease ( Tan et al., 2019 ). It must also be emphasized that myeloid cells are also recruited to the site of inflammation via CCL2, CCL20 and IL-1β ( Duangkhae et al., 2018 ).…”

Seroepidemiologic study on convalescent sera from dengue fever patients in Jinghong, Yunnan

“…DENV is mainly transmitted by Aedes aegypti and Aedes albopictus. It is widely prevalent in more than 100 countries in tropical and subtropical areas ( Tan et al., 2019 ). The clinical classification of DENV-infected disease includes two categories: dengue fever (DF), and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) that is defined as severe dengue ( Lin et al., 2017 ).…”