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Mechanism of chlorogenic acid in alveolar macrophage polarization in Klebsiella pneumoniae‐induced pneumonia
Ist Teil von
Journal of leukocyte biology, 2022-07, Vol.112 (1), p.9-21
Erscheinungsjahr
2022
Quelle
Wiley Online Library
Beschreibungen/Notizen
Chlorogenic acid (CA) has been discovered to regulate macrophage polarization in pneumonia. This study aims to analyze the functional mechanism of CA in alveolar macrophage (AM) polarization and provide a theoretical basis for treatment of Klebsiella pneumoniae (Kp)‐induced pneumonia. Mice were infected with Kp, and treated with CA and silent information regulator 1 (SIRT1) inhibitor (Selisistat). Mouse survival rate was recorded and bacterial burden was detected. AM polarization and pathologic change of lung tissues were evaluated. Expressions of SIRT1 and HMGB1 and cytokine levels were detected. MH‐S cells were infected with Kp to establish the pneumonia cell model, followed by transfection of si‐SIRT1 and HMGB1 overexpression vector. The HMGB1 expression in the nucleus and cytoplasm was detected. HMGB1 subcellular localization and HMGB1 acetylation level were detected. Kp led to high death rates, SIRT down‐regulation and increases in inflammatory factor level and bacterial burden, and promoted M1 polarization. CA treatment improved mouse survival rate and promoted M2 polarization and SIRT1 expression. SIRT1 decreased HMGB1 acetylation level to inhibit nuclear to the cytoplasm translocation. Silencing SIRT1 or HMGB1 overexpression reversed the effect of CA on Kp‐induced pneumonia. Overall, CA activated SIRT1 to inhibit HMGB1 acetylation level and nuclear translocation, thereby promoting M2 polarization in AMs and alleviating Kp‐induced pneumonia.
Graphical
Examines the functional mechanism of CA in AM polarization in detail and provides a theoretical basis for treatment of Klebsiella pneumoniae (Kp)‐induced pneumonia.