title: Protection against reperfusion lung injury via aborgating multiple signaling cascades by trichostatin A.
abstract: Trichostatin A (TSA) is a histone deacetylase inhibitor with anti-inflammatory effects. Nonetheless, little information is available about the effect of TSA in ischemia-reperfusion (IR)-induced lung injury. In a perfused rat lung model, IR was induced by 40min of ischemia followed by 60min of reperfusion. The rat lungs were randomly divided into several groups including control, control+TSA (0.1mg/kg), IR, and IR+various dosages of TSA (0.05, 0.075, 0.1mg/kg). Bronchoalveolar lavage fluids and lung tissues were obtained and examined at the end of the experiment. TSA dose-dependently diminished IR-induced increased vascular permeability and edema, pulmonary artery pressure, and histological changes in the lungs. Additionally, TSA suppressed lavage tumor necrosis factor-α and cytokine-induced neutrophil chemoattractant concentrations, cell infiltration, and myeloperoxidase-positive cells in the lung tissue. Furthermore, TSA attenuated the phosphorylation of extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase, degradation of the inhibitor of nuclear factor (NF)-κB, and nuclear NF-κB levels. TSA also decreased poly (ADP-ribose) polymerase but enhanced acetylated histone H3 acetylation, Bcl-2, and mitogen-activated protein kinase phosphatase-1 (MKP-1) expression in IR lung tissue. Therefore, TSA exerted a protective effect on IR-induced lung injury via increasing histone acetylation and MKP-1 protein expression, repressing NF-κB, mitogen-activated protein kinase, and apoptosis signaling pathways.
authors.affiliation: Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hsian-He
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shih-En
authors.initials: SE
authors.lastname: Tang
authors.affiliation: Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan.
authors.forename: Geng-Chin
authors.initials: GC
authors.lastname: Wu
authors.affiliation: Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Li
authors.affiliation: Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan. Electronic address: kun@mail.ndmctsgh.edu.tw.
authors.forename: Kun-Lun
authors.initials: KL
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address: d1204812@mail.ndmctsgh.edu.tw.
authors.forename: Shi-Jye
authors.initials: SJ
authors.lastname: Chu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D055371:Acute Lung Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D062186:Arterial Pressure / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054360:Chemokine CXCL1 / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C012589:trichostatin A; D020928:Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat
keywords: Acute lung injury; Ischemia-reperfusion (IR); Mitogen-activated protein kinase (MAPK); Mitogen-activated protein kinase phosphatase-1 (MKP-1); Trichostatin A (TSA)