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GSK2656157, a PERK inhibitor, reduced LPS-induced IL-1ß production through inhibiting Caspase 1 activation in macrophage-like J774.1 cells.
Ando, Takashi; Komatsu, Takayuki; Naiki, Yoshikazu; Takahashi, Kazuko; Yokochi, Takashi; Watanabe, Daisuke; Koide, Naoki.
Afiliación
  • Ando T; a Department of Dermatology , Aichi Medical University School of Medicine , Nagakute , Japan ;
  • Komatsu T; b Department of Microbiology and Immunology , Aichi Medical University School of Medicine , Nagakute , Japan.
  • Naiki Y; b Department of Microbiology and Immunology , Aichi Medical University School of Medicine , Nagakute , Japan.
  • Takahashi K; b Department of Microbiology and Immunology , Aichi Medical University School of Medicine , Nagakute , Japan.
  • Yokochi T; b Department of Microbiology and Immunology , Aichi Medical University School of Medicine , Nagakute , Japan.
  • Watanabe D; a Department of Dermatology , Aichi Medical University School of Medicine , Nagakute , Japan ;
  • Koide N; b Department of Microbiology and Immunology , Aichi Medical University School of Medicine , Nagakute , Japan.
Immunopharmacol Immunotoxicol ; 38(4): 298-302, 2016 Aug.
Article en En | MEDLINE | ID: mdl-27251848
IL-1ß is one of the inflammatory cytokines and is cleaved from pro-IL-1ß proteolytically by activated Caspase 1. For the activation of Caspase 1, inflammasome was formed by two signals, what is called, priming and triggering signals. In this study, it was found that mouse macrophage J774.1 cells, when treated by single large amount of lipopolysaccharide (LPS), produced a significant amount of IL-1ß. On the other hand, IL-1ß production was not detected when treated by a single, small amount of LPS. Then, focusing on endoplasmic reticulum (ER) stress response among stress responses induced by a large amount of LPS, when GSK2656157, a PERK inhibitor, was used for inhibition of ER stress, GSK2656157 reduced IL-1ß production dose-dependently. Next, when Thapsigargin, an ER stress reagent, was added with LPS, IL-1ß production increased more than by LPS alone. Thus, these results suggested that ER stress was involved in LPS-induced IL-1ß production. When the activation of Caspase 1 was examined by fluorescence activated cell sorter analysis, it was found that GSK2656157 inhibited LPS-induced Caspase 1 activation. Further, it was confirmed that GSK2656157 did not affect LPS-induced TNF-α production and activation of NF-κB and specifically inhibited the PERK/eIF-2α pathway. Therefore, it was found that GSK2656157 specifically inhibited ER stress induced by large amount of LPS and reduced LPS-induced IL-1ß production through inhibition of Caspase 1 activation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenina / Lipopolisacáridos / EIF-2 Quinasa / Caspasa 1 / Interleucina-1beta / Indoles / Macrófagos Límite: Animals Idioma: En Revista: Immunopharmacol Immunotoxicol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA / TOXICOLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenina / Lipopolisacáridos / EIF-2 Quinasa / Caspasa 1 / Interleucina-1beta / Indoles / Macrófagos Límite: Animals Idioma: En Revista: Immunopharmacol Immunotoxicol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA / TOXICOLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido