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Aqueous extract of Descuraniae Semen attenuates lipopolysaccharide-induced inflammation by inhibiting ER stress and WNK4-SPAK-NKCC1 pathway.
Hsieh, Po-Chun; Huang, Kun-Lun; Peng, Chung-Kan; Wu, Yao-Kuang; Liu, Guan-Ting; Kuo, Chan-Yen; Wang, Ming-Chieh; Lan, Chou-Chin.
Afiliación
  • Hsieh PC; Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
  • Huang KL; Department of Chinese Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Peng CK; Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
  • Wu YK; Division of Pulmonary and Critical Care, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.
  • Liu GT; Division of Pulmonary and Critical Care, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.
  • Kuo CY; Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • Wang MC; Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
  • Lan CC; School of Medicine, Tzu Chi University, Hualien, Taiwan.
J Cell Mol Med ; 28(15): e18589, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39135202
ABSTRACT
Sepsis causes systemic inflammatory responses and acute lung injury (ALI). Despite modern treatments, sepsis-related ALI mortality remains high. Aqueous extract of Descuraniae Semen (AEDS) exerts anti-endoplasmic reticulum (ER) stress, antioxidant and anti-inflammatory effects. AEDS alleviates inflammation and oedema in ALI. Sodium-potassium-chloride co-transporter isoform 1 (NKCC1) is essential for regulating alveolar fluid and is important in ALI. The NKCC1 activity is regulated by upstream with-no-lysine kinase-4 (WNK4) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). This study aimed to investigate the effects of AEDS on lipopolysaccharide (LPS)-induced ALI model in A549 cells, considering the regulation of ER stress, WNK4-SPAK-NKCC1 cascades, inflammation and apoptosis. Cell viability was investigated by the CCK-8 assay. The expressions of the proteins were assessed by immunoblotting analysis assays. The levels of pro-inflammatory cytokines were determined by ELISA. The expression of cytoplasmic Ca2+ in A549 cells was determined using Fluo-4 AM. AEDS attenuates LPS-induced inflammation, which is associated with increased pro-inflammatory cytokine expression and activation of the WNK4-SPAK-NKCC1 pathway. AEDS inhibits the WNK4-SPAK-NKCC1 pathway by regulating of Bcl-2, IP3R and intracellular Ca2+. WNK4 expression levels are significantly higher in the WNK4-overexpressed transfected A549 cells and significantly decrease after AEDS treatment. AEDS attenuates LPS-induced inflammation by inhibiting the WNK4-SPAK-NKCC1 cascade. Therefore, AEDS is regarded as a potential therapeutic agent for ALI.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Lipopolisacáridos / Proteínas Serina-Treonina Quinasas / Estrés del Retículo Endoplásmico / Miembro 2 de la Familia de Transportadores de Soluto 12 / Inflamación Límite: Humans Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Lipopolisacáridos / Proteínas Serina-Treonina Quinasas / Estrés del Retículo Endoplásmico / Miembro 2 de la Familia de Transportadores de Soluto 12 / Inflamación Límite: Humans Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido