Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice

S. E.I. Van Der Wal, M. Vaneker, M. Kox, G. Braak, H. W.H. Van Hees, I. A. Van Den Brink, F. M. Van De Pol, L. M. Heunks, J. G. Van Der Hoeven, L. A.B. Joosten, K. C.P. Vissers, G. J. Scheffer

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-κB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 signaling and NF-κB. In the present study, we investigated the role of RVT in MV-induced inflammation in mice. Methods RVT (10 mg/kg, 20 mg/kg and 40 mg/kg) or vehicle was intraperitoneally administered 1 h before start of MV (4 h, tidal volume 8 ml/kg, positive end-expiratory pressure 1,5 cmH2O and FiO2 0.4). Blood and lungs were harvested for cytokine analysis. DNA binding activity of transcription factor NF-κB was measured in lung homogenates. Results MV resulted in elevated pulmonary concentrations of IL-1β, IL-6, keratinocyte-derived chemokine (KC) and NF-κB DNA-binding activity. RVT at 10, 20 and 40 mg/kg reduced NF-κB's DNA-binding activity following MV compared with ventilated controls. However, no differences in cytokine release were found between RVT-treated and control ventilated mice. Similarly, in plasma, MV resulted in elevated concentrations of TNF-α, KC and IL-6, but RVT did not affect cytokine levels. Conclusions RVT abrogates the MV-induced increase in pulmonary NF-κB activity but does not attenuate cytokine levels. This implies a less prominent role for NF-κB in MV-induced inflammation than previously assumed.

Original languageEnglish
Pages (from-to)487-494
Number of pages8
JournalActa Anaesthesiologica Scandinavica
Volume58
Issue number4
DOIs
Publication statusPublished - 1 Jan 2014

Cite this

Van Der Wal, S. E. I., Vaneker, M., Kox, M., Braak, G., Van Hees, H. W. H., Van Den Brink, I. A., ... Scheffer, G. J. (2014). Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice. Acta Anaesthesiologica Scandinavica, 58(4), 487-494. https://doi.org/10.1111/aas.12276
Van Der Wal, S. E.I. ; Vaneker, M. ; Kox, M. ; Braak, G. ; Van Hees, H. W.H. ; Van Den Brink, I. A. ; Van De Pol, F. M. ; Heunks, L. M. ; Van Der Hoeven, J. G. ; Joosten, L. A.B. ; Vissers, K. C.P. ; Scheffer, G. J. / Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice. In: Acta Anaesthesiologica Scandinavica. 2014 ; Vol. 58, No. 4. pp. 487-494.
@article{e0073c39887f45168958ba6955f3f8ec,
title = "Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice",
abstract = "Background Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-κB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 signaling and NF-κB. In the present study, we investigated the role of RVT in MV-induced inflammation in mice. Methods RVT (10 mg/kg, 20 mg/kg and 40 mg/kg) or vehicle was intraperitoneally administered 1 h before start of MV (4 h, tidal volume 8 ml/kg, positive end-expiratory pressure 1,5 cmH2O and FiO2 0.4). Blood and lungs were harvested for cytokine analysis. DNA binding activity of transcription factor NF-κB was measured in lung homogenates. Results MV resulted in elevated pulmonary concentrations of IL-1β, IL-6, keratinocyte-derived chemokine (KC) and NF-κB DNA-binding activity. RVT at 10, 20 and 40 mg/kg reduced NF-κB's DNA-binding activity following MV compared with ventilated controls. However, no differences in cytokine release were found between RVT-treated and control ventilated mice. Similarly, in plasma, MV resulted in elevated concentrations of TNF-α, KC and IL-6, but RVT did not affect cytokine levels. Conclusions RVT abrogates the MV-induced increase in pulmonary NF-κB activity but does not attenuate cytokine levels. This implies a less prominent role for NF-κB in MV-induced inflammation than previously assumed.",
author = "{Van Der Wal}, {S. E.I.} and M. Vaneker and M. Kox and G. Braak and {Van Hees}, {H. W.H.} and {Van Den Brink}, {I. A.} and {Van De Pol}, {F. M.} and Heunks, {L. M.} and {Van Der Hoeven}, {J. G.} and Joosten, {L. A.B.} and Vissers, {K. C.P.} and Scheffer, {G. J.}",
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Van Der Wal, SEI, Vaneker, M, Kox, M, Braak, G, Van Hees, HWH, Van Den Brink, IA, Van De Pol, FM, Heunks, LM, Van Der Hoeven, JG, Joosten, LAB, Vissers, KCP & Scheffer, GJ 2014, 'Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice' Acta Anaesthesiologica Scandinavica, vol. 58, no. 4, pp. 487-494. https://doi.org/10.1111/aas.12276

Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice. / Van Der Wal, S. E.I.; Vaneker, M.; Kox, M.; Braak, G.; Van Hees, H. W.H.; Van Den Brink, I. A.; Van De Pol, F. M.; Heunks, L. M.; Van Der Hoeven, J. G.; Joosten, L. A.B.; Vissers, K. C.P.; Scheffer, G. J.

In: Acta Anaesthesiologica Scandinavica, Vol. 58, No. 4, 01.01.2014, p. 487-494.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice

AU - Van Der Wal, S. E.I.

AU - Vaneker, M.

AU - Kox, M.

AU - Braak, G.

AU - Van Hees, H. W.H.

AU - Van Den Brink, I. A.

AU - Van De Pol, F. M.

AU - Heunks, L. M.

AU - Van Der Hoeven, J. G.

AU - Joosten, L. A.B.

AU - Vissers, K. C.P.

AU - Scheffer, G. J.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-κB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 signaling and NF-κB. In the present study, we investigated the role of RVT in MV-induced inflammation in mice. Methods RVT (10 mg/kg, 20 mg/kg and 40 mg/kg) or vehicle was intraperitoneally administered 1 h before start of MV (4 h, tidal volume 8 ml/kg, positive end-expiratory pressure 1,5 cmH2O and FiO2 0.4). Blood and lungs were harvested for cytokine analysis. DNA binding activity of transcription factor NF-κB was measured in lung homogenates. Results MV resulted in elevated pulmonary concentrations of IL-1β, IL-6, keratinocyte-derived chemokine (KC) and NF-κB DNA-binding activity. RVT at 10, 20 and 40 mg/kg reduced NF-κB's DNA-binding activity following MV compared with ventilated controls. However, no differences in cytokine release were found between RVT-treated and control ventilated mice. Similarly, in plasma, MV resulted in elevated concentrations of TNF-α, KC and IL-6, but RVT did not affect cytokine levels. Conclusions RVT abrogates the MV-induced increase in pulmonary NF-κB activity but does not attenuate cytokine levels. This implies a less prominent role for NF-κB in MV-induced inflammation than previously assumed.

AB - Background Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-κB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 signaling and NF-κB. In the present study, we investigated the role of RVT in MV-induced inflammation in mice. Methods RVT (10 mg/kg, 20 mg/kg and 40 mg/kg) or vehicle was intraperitoneally administered 1 h before start of MV (4 h, tidal volume 8 ml/kg, positive end-expiratory pressure 1,5 cmH2O and FiO2 0.4). Blood and lungs were harvested for cytokine analysis. DNA binding activity of transcription factor NF-κB was measured in lung homogenates. Results MV resulted in elevated pulmonary concentrations of IL-1β, IL-6, keratinocyte-derived chemokine (KC) and NF-κB DNA-binding activity. RVT at 10, 20 and 40 mg/kg reduced NF-κB's DNA-binding activity following MV compared with ventilated controls. However, no differences in cytokine release were found between RVT-treated and control ventilated mice. Similarly, in plasma, MV resulted in elevated concentrations of TNF-α, KC and IL-6, but RVT did not affect cytokine levels. Conclusions RVT abrogates the MV-induced increase in pulmonary NF-κB activity but does not attenuate cytokine levels. This implies a less prominent role for NF-κB in MV-induced inflammation than previously assumed.

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U2 - 10.1111/aas.12276

DO - 10.1111/aas.12276

M3 - Article

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SP - 487

EP - 494

JO - Acta Anæsthesiologica Scandinavica

JF - Acta Anæsthesiologica Scandinavica

SN - 0001-5172

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