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

doi:10.1186/cc6995

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

Research output: Contribution to journal › Article › peer-review

36 Citations (Scopus)

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 (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.

Original language	English
Article number	R108
Journal	Critical Care
Volume	12
Issue number	4
DOIs	https://doi.org/10.1186/cc6995
Publication status	Published - 2008 Aug 22

Bibliographical note

Funding Information:
This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2004-003-E00088).

ASJC Scopus subject areas

Critical Care and Intensive Care Medicine

Access to Document

10.1186/cc6995

Cite this

@article{32bea2a521a344ba9be49b862acc7227,

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

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.",

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

note = "Funding Information: This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2004-003-E00088).",

year = "2008",

month = aug,

day = "22",

doi = "10.1186/cc6995",

language = "English",

volume = "12",

journal = "Critical Care",

issn = "1364-8535",

publisher = "BioMed Central",

number = "4",

}

TY - JOUR

T1 - Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury

AU - Kim, Je Hyeong

AU - Suk, Min Hyun

AU - Yoon, Dae Wui

AU - Kim, Hye Young

AU - Jung, Ki Hwan

AU - Kang, Eun Hae

AU - Lee, Sung Yong

AU - Lee, Sang Yeub

AU - Suh, In Bum

AU - Shin, Chol

AU - Shim, Jae Jeong

AU - In, Kwang Ho

AU - Yoo, Se Hwa

AU - Kang, Kyung Ho

N1 - Funding Information: This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2004-003-E00088).

PY - 2008/8/22

Y1 - 2008/8/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=51349090137&partnerID=8YFLogxK

U2 - 10.1186/cc6995

DO - 10.1186/cc6995

M3 - Article

C2 - 18718025

AN - SCOPUS:51349090137

SN - 1364-8535

VL - 12

JO - Critical Care

JF - Critical Care

IS - 4

M1 - R108

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this