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2.
FASEB J ; 33(3): 3392-3403, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30383446

RESUMO

Allergic conjunctivitis (AC) is one of the most common ocular surface diseases in the world. In AC, T helper type 2 (Th2) immune responses play central roles in orchestrating inflammatory responses. However, the roles of lipid mediators in the onset and progression of AC remain to be fully explored. Although previous reports have shown the beneficial effects of supplementation of ω-3 fatty acids in asthma or atopic dermatitis, the underlying molecular mechanisms are poorly understood. In this study, a diet rich in ω-3 fatty acids alleviated AC symptoms in both early and late phases without affecting Th2 immune responses, but rather by altering the lipid mediator profiles. The ω-3 fatty acids completely suppressed scratching behavior toward the eyes, an allergic reaction provoked by itch. Although total serum IgE levels and the expression levels of Th2 cytokines and chemokines in the conjunctiva were not altered by ω-3 fatty acids, eosinophil infiltration into the conjunctiva was dramatically suppressed. The levels of ω-6-derived proinflammatory lipid mediators, including those with chemoattractant properties for eosinophils, were markedly reduced in the conjunctivae of ω-3 diet-fed mice. Dietary ω-3 fatty acids can alleviate a variety of symptoms of AC by altering the lipid mediator profile.-Hirakata, T., Lee, H.-C., Ohba, M., Saeki, K., Okuno, T., Murakami, A., Matsuda, A., Yokomizo, T. Dietary ω-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating Th2 immune responses.


Assuntos
Conjuntivite Alérgica/imunologia , Ácidos Graxos Ômega-3/imunologia , Lipídeos/imunologia , Células Th2/imunologia , Animais , Asma/imunologia , Quimiocinas/imunologia , Citocinas/imunologia , Dieta/métodos , Eicosanoides/imunologia , Eosinófilos/imunologia , Feminino , Imunoglobulina E/imunologia , Camundongos , Camundongos Endogâmicos BALB C
3.
J Antibiot (Tokyo) ; 70(4): 443-447, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27756911

RESUMO

Caliciviruses are contagious pathogens of humans and various animals. They are the most common cause of viral gastroenteritis in humans, and can cause lethal diseases in domestic animals such as cats, rabbits and immunocompromised mice. In this study, we conducted cytopathic effect-based screening of 2080 selected compounds from our in-house library to find antiviral compounds against three culturable caliciviruses: feline calicivirus, murine norovirus (MNV) and porcine sapovirus (PoSaV). We identified active six compounds, of which two compounds, both related to theaflavins, showed broad antiviral activities against all three caliciviruses; three compounds (abamectin, a mixture of avermectin B1a and B1b; avermectin B1a; and (-)-epigallocatechin gallate hydrate) were effective against PoSaV only; and a heterocyclic carboxamide derivative (BFTC) specifically inhibited MNV infectivity in cell cultures. Further studies of the antiviral mechanism and structure-activity relationship of theaflavins suggested the following: (1) theaflavins worked before the viral entry step; (2) the effect of theaflavins was time- and concentration-dependent; and (3) the hydroxyl groups of the benzocycloheptenone ring were probably important for the anti-calicivirus activity of theaflavins. Theaflavins could be used for the calicivirus research, and as potential disinfectants and antiviral reagents to prevent and control calicivirus infections in animals and humans.


Assuntos
Antivirais/farmacologia , Biflavonoides/farmacologia , Caliciviridae/efeitos dos fármacos , Catequina/farmacologia , Flavinas/farmacologia , Animais , Infecções por Caliciviridae , Calicivirus Felino/efeitos dos fármacos , Catequina/análogos & derivados , Gatos , Efeito Citopatogênico Viral/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Camundongos , Norovirus/efeitos dos fármacos , Estrutura Quaternária de Proteína , Sapovirus/efeitos dos fármacos , Relação Estrutura-Atividade
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