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p38 MAPK inhibitors in COPD

Patricia Macedo, Joann Rhodes, Iain Kilty, Peter Barnes, Louise Donnelly
European Respiratory Journal 2012 40: P3714; DOI:
Patricia Macedo
1Airway Diseases, National Heart and Lung Institute, Imperial College, London, United Kingdom
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Joann Rhodes
2Pfizer, Pfizer Inc, Cambridge, MA, United States
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Iain Kilty
2Pfizer, Pfizer Inc, Cambridge, MA, United States
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Peter Barnes
1Airway Diseases, National Heart and Lung Institute, Imperial College, London, United Kingdom
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Louise Donnelly
1Airway Diseases, National Heart and Lung Institute, Imperial College, London, United Kingdom
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Abstract

p38 MAPK signalling upregulates inflammation and is known to be increased in COPD. This study investigated whether p38 inhibitors PF75 and PF32 suppressed release of inflammatory cytokines from macrophage-lineage cells.

Peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM) were isolated from non-smokers (NS), smokers (S) and COPD patients. Cells were pre-treated with either p38 inhibitor or dexamethasone (DEX) prior to stimulation with LPS. Cell media was harvested at 24h and cytokine release (IL-6, CXCL8, IL-10 and TNF) measured by ELISA.

Both p38 inhibitors and DEX suppressed cytokine release in a concentration-dependent manner in PBMC and MDM. There were no differences between subject groups.

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EC50 values (nM) for DEX, PF75 and PF32 on cytokine release

p38 inhibitors suppress release of inflammatory cytokines and may have a therapeutic role in COPD.

  • COPD - mechanism
  • Inflammation
  • Monocyte / Macrophage
  • © 2012 ERS
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p38 MAPK inhibitors in COPD
Patricia Macedo, Joann Rhodes, Iain Kilty, Peter Barnes, Louise Donnelly
European Respiratory Journal Sep 2012, 40 (Suppl 56) P3714;

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p38 MAPK inhibitors in COPD
Patricia Macedo, Joann Rhodes, Iain Kilty, Peter Barnes, Louise Donnelly
European Respiratory Journal Sep 2012, 40 (Suppl 56) P3714;
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