title: Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury.
abstract: BACKGROUND
  Poly (ADP-ribose) polymerase (PARP) participates in inflammation by cellular necrosis and the nuclear factor-kappa-B (NF-kappaB)-dependent transcription. The purpose of this study was to examine the roles of PARP in ventilator-induced lung injury (VILI) in normal mice lung.
  
  
  METHODS
  Male C57BL/6 mice were divided into four groups: sham tracheostomized (sham), lung-protective ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory pressure (PIP) 15 cm H2O + positive end-expiratory pressure (PEEP) 3 cm H2O + 90 breaths per minute for the LPV group and PIP 40 cm H2O + PEEP 0 cm H2O + 90 breaths per minute for the VILI and PJ34+VILI groups. After 2 hours of MV, acute lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and dynamic compliance (CD) were recorded. Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX) in the bronchoalveolar lavage fluid and NF-kappaB DNA-binding activity in tissue homogenates were measured.
  
  
  RESULTS
  The VILI group showed higher ALI score, W/D weight ratio, MPO activity, NOX, and concentrations of TNF-alpha and IL-6 along with lower CD than the sham and LPV groups (P < 0.05). In the PJ34+VILI group, PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and pulmonary dynamics (P < 0.05). NF-kappaB activity was increased in the VILI group as compared with the sham and LPV groups (P < 0.05) and was decreased in the PJ34+VILI group as compared with the VILI group (P = 0.009). Changes in all parameters were closely correlated with the PARP activity (P < 0.05).
  
  
  CONCLUSIONS
  Overactivation of PARP plays an important role in the inflammatory and transcriptional pathogenesis of VILI, and PARP inhibition has potentially beneficial effects on the prevention and treatment of VILI.
authors: Division of Pulmonary, Sleep and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, 516, Gojan 1-dong, Danwon-gu, Ansan 425-707, Republic of Korea.
authors: Je Hyeong
authors: JH
authors: Kim
authors: Min Hyun
authors: MH
authors: Suk
authors: Dae Wui
authors: DW
authors: Yoon
authors: Hye Young
authors: HY
authors: Kim
authors: Ki Hwan
authors: KH
authors: Jung
authors: Eun Hae
authors: EH
authors: Kang
authors: Sung Yong
authors: SY
authors: Lee
authors: Sang Yeub
authors: SY
authors: Lee
authors: In Bum
authors: IB
authors: Suh
authors: Chol
authors: C
authors: Shin
authors: Jae Jeong
authors: JJ
authors: Shim
authors: Kwang Ho
authors: KH
authors: In
authors: Se Hwa
authors: SH
authors: Yoo
authors: Kyung Ho
authors: KH
authors: Kang
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D018836:Inflammation Mediators / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000502:physiology*; D012121:Respiration, Artificial / Q000009:adverse effects*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*; D055397:Ventilator-Induced Lung Injury / Q000201:enzymology* / Q000209:etiology / Q000473:pathology
chemical_list: D018836:Inflammation Mediators; D011065:Poly(ADP-ribose) Polymerases