Examinando por Autor "Tabares Guevara, Jorge H."
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Ítem Asymptomatic Herpes Simplex Virus Type 1 Infection Causes an Earlier Onset and More Severe Experimental Autoimmune Encephalomyelitis(Frontiers Media S.A., 2021-02) Duarte, Luisa F.; Altamirano Lagos, María J.; Tabares Guevara, Jorge H.; Opazo, Ma. Cecilia; Díaz, Máximo; Navarrete, Romina; Muza, Catalina; Vallejos, Omar P.; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.Multiple sclerosis (MS) is an increasingly prevalent progressive autoimmune and debilitating chronic disease that involves the detrimental recognition of central nervous system (CNS) antigens by the immune system. Although significant progress has been made in the last decades on the biology of MS and the identification of novel therapies to treat its symptoms, the etiology of this disease remains unknown. However, recent studies have suggested that viral infections may contribute to disease onset. Interestingly, a potential association between herpes simplex virus type 1 (HSV-1) infection and MS has been reported, yet a direct relationship among both has not been conclusively demonstrated. Experimental autoimmune encephalomyelitis (EAE) recapitulates several aspects of MS in humans and is widely used to study this disease. Here, we evaluated the effect of asymptomatic brain infection by HSV-1 on the onset and severity of EAE in C57BL/6 mice. We also evaluated the effect of infection with an HSV-1-mutant that is attenuated in neurovirulence and does not cause encephalitis. Importantly, we observed more severe EAE in mice previously infected either, with the wild-type (WT) or the mutant HSV-1, as compared to uninfected control mice. Also, earlier EAE onset was seen after WT virus inoculation. These findings support the notion that a previous exposure to HSV-1 can accelerate and enhance EAE, which suggests a potential contribution of asymptomatic HSV-1 to the onset and severity of MS. © Copyright © 2021 Duarte, Altamirano-Lagos, Tabares-Guevara, Opazo, Díaz, Navarrete, Muza, Vallejos, Riedel, Bueno, Kalergis and González.Ítem IL-10-Dependent Amelioration of Chronic Inflammatory Disease by Microdose Subcutaneous Delivery of a Prototypic Immunoregulatory Small Molecule(Frontiers Media S.A., 2021-07) Tabares Guevara, Jorge H.; Jaramillo, Julio C.; Ospina Quintero, Laura; Piedrahíta Ochoa, Christian A.; García Valencia, Natalia; Bautista Erazo, David E.; Caro Gómez, Erika; Covián, Camila; Retamal Díaz, Angello; Duarte, Luisa F.; González, Pablo A.; Bueno, Susan M.; Riedel, Claudia A.; Kalergis, Alexis M.; Ramírez Pineda, José R.One of the interventional strategies to reestablish the immune effector/regulatory balance, that is typically altered in chronic inflammatory diseases (CID), is the reinforcement of endogenous immunomodulatory pathways as the one triggered by interleukin (IL)-10. In a recent work, we demonstrated that the subcutaneous (sc) administration of an IL-10/Treg-inducing small molecule-based formulation, using a repetitive microdose (REMID) treatment strategy to preferentially direct the effects to the regional immune system, delays the progression of atherosclerosis. Here we investigated whether the same approach using other IL-10-inducing small molecule, such as the safe, inexpensive, and widely available polyphenol curcumin, could induce a similar protective effect in two different CID models. We found that, in apolipoprotein E deficient mice, sc treatment with curcumin following the REMID strategy induced atheroprotection that was not consequence of its direct systemic lipid-modifying or antioxidant activity, but instead paralleled immunomodulatory effects, such as reduced proatherogenic IFNγ/TNFα-producing cells and increased atheroprotective FOXP3+ Tregs and IL-10-producing dendritic and B cells. Remarkably, when a similar strategy was used in the neuroinflammatory model of experimental autoimmune encephalomyelitis (EAE), significant clinical and histopathological protective effects were evidenced, and these were related to an improved effector/regulatory cytokine balance in restimulated splenocytes. The essential role of curcumin-induced IL-10 for neuroprotection was confirmed by the complete abrogation of the clinical effects in IL-10-deficient mice. Finally, the translational therapeutic prospection of this strategy was evidenced by the neuroprotection observed in mice starting the treatment one week after disease triggering. Collectively, results demonstrate the power of a simple natural IL-10-inducing small molecule to tackle chronic inflammation, when its classical systemic and direct pharmacological view is shifted towards the targeting of regional immune cells, in order to rationally harness its immunopharmacological potential. This shift implies that many well-known IL-10-inducing small molecules could be easily reformulated and repurposed to develop safe, innovative, and accessible immune-based interventions for CID. © Copyright © 2021 Tabares-Guevara, Jaramillo, Ospina-Quintero, Piedrahíta-Ochoa, García-Valencia, Bautista-Erazo, Caro-Gómez, Covián, Retamal-Díaz, Duarte, González, Bueno, Riedel, Kalergis and Ramírez-Pineda.