Research

Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury

Je Hyeong Kim¹ , Min Hyun Suk² , Dae Wui Yoon¹ , Hye Young Kim¹ , Ki Hwan Jung¹ , Eun Hae Kang³ , Sung Yong Lee⁴ , Sang Yeub Lee³ , In Bum Suh⁵ , Chol Shin¹ , Jae Jeong Shim⁴ , Kwang Ho In³ , Se Hwa Yoo³ and Kyung Ho Kang⁴

¹  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

²  Department of Nursing, College of Medicine, Pochon CHA University, 222 Yatap-dong, Bundang-gu, Sungnam 463-712, Republic of Korea

³  Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Republic of Korea

⁴  Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, 80, Guro 2-dong, Guro-gu, Seoul 152-703, Republic of Korea

⁵  Department of Clinical Pathology, College of Medicine, Kangwon National University, 26, Kangwondaehak-no, Chuncheon 200-947, Republic of Korea

author email corresponding author email

Critical Care 2008, 12:R108doi:10.1186/cc6995

Published:	22 August 2008

See related letter by Vaneker et al., http://ccforum.com/content/12/5/431

Abstract

Introduction

Poly (ADP-ribose) polymerase (PARP) participates in inflammation by cellular necrosis and the nuclear factor-kappa-B (NF-κB)-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 (C_D) were recorded. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NO_X) in the bronchoalveolar lavage fluid and NF-κB DNA-binding activity in tissue homogenates were measured.

Results

The VILI group showed higher ALI score, W/D weight ratio, MPO activity, NO_X, and concentrations of TNF-α and IL-6 along with lower C_D 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-κB 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).

Conclusion

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.