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

Je Hyeong Kim, Min Hyun Suk, Dae Wui Yoon, Hye Young Kim, Ki Hwan Jung, Eun Hae Kang, Sung Yong Lee, Sang Yeub Lee, In Bum Suh, Chol Shin, Jae Jeong Shim, Kwang Ho In, Se Hwa Yoo, Kyung Ho Kang

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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 (CD) were recorded. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX) 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, NOX, and concentrations of TNF-α 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-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.

Original languageEnglish
Article numberR108
JournalCritical Care
Volume12
Issue number4
DOIs
Publication statusPublished - 2008 Aug 22

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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    Kim, J. H., Suk, M. H., Yoon, D. W., Kim, H. Y., Jung, K. H., Kang, E. H., Lee, S. Y., Lee, S. Y., Suh, I. B., Shin, C., Shim, J. J., In, K. H., Yoo, S. H., & Kang, K. H. (2008). Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury. Critical Care, 12(4), [R108]. https://doi.org/10.1186/cc6995