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Clinical interventions in COPD
P143 NF-kappa B (NF-κB) and activator protein-1 (AP-1) DNA binding in the quadriceps of COPD patients
  1. S A Natanek1,
  2. R C J Langen2,
  3. H R Gosker2,
  4. G S Marsh1,
  5. I Slot2,
  6. N S Hopkinson1,
  7. W D-C Man1,
  8. P R Kemp3,
  9. J Moxham4,
  10. A M W J Schols2,
  11. M I Polkey1
  1. 1NIHR Respiratory Biomedical Research Unit of the Royal Brompton and Harefield NHS Foundation Trust and National Heart & Lung Institute, Imperial College London, London, UK
  2. 2NUTRIM School for Nutrition, Toxicology & Metabolism, Maastricht University, Maastricht, the Netherlands
  3. 3National Heart & Lung Institute, Imperial College London, London, UK
  4. 4Guy's, King's and St Thomas' School of Medicine, London, UK

Abstract

Introduction Animal work implicates NF-κB and AP-1 activation in muscle atrophy (Cai et al, 2004 and Costelli et al, 2005). Prior study of seven COPD patients with a low BMI and seven COPD patients with a normal BMI suggested that NF-κB DNA binding was increased in the former (Agusti et al, 2004) although others have not demonstrated NF-κB activation in COPD muscle (Plant et al, 2009).

Aim Evaluate NF-κB and AP-1 activation in the quadriceps of patients with stable COPD in relation to muscle atrophy.

Methods 114 COPD patients and 30 healthy age-matched controls underwent measurements of lung function and bioelectrical impedance to determine fat-free mass index (FFMI) and a percutaneous Bergstrom needle biopsy of the quadriceps. Transcription factor ELISAs were performed on nuclear extracts from quadriceps muscle to measure quantities of NF-κB P50, P65, and AP-1 c-jun subunits in muscle nuclei capable of binding DNA. Immunohistochemistry was used to determine type I and II fibre cross-sectional area (CSA) from muscle sections.

Results There was no evidence of increased quantities of muscle nuclear P65 or P50 binding DNA in patients compared with controls and the quantity of muscle nuclear AP-1 c-jun binding DNA was lower in patients than controls (336 (174,513)RLU vs 508 (284,846)RLU, p=0.01). Patients with low FFMI (≤15 and 16 kg/m2 for females and males respectively, n=54) did not have increased quantities of P65, P50 or c-jun binding DNA compared with patients with normal FFMI (n=60, (286 (171,407) vs 260 (176,376) RLU p=0.94, 880 (400,1373) vs 1064 (654,1586) RLU p=0.33 and 313 (155,484) vs 353 (181,570) RLU p=0.42 respectively). There were no correlations between quantities of the transcription factors binding DNA and quadriceps type I or II fibre CSA or type I, IIa or IIx fibre proportions.

Conclusion NF-κB and AP-1 DNA-binding were not increased in the quadriceps of patients with stable COPD compared to controls and did not predict reduced FFMI or quadriceps fibre size, nor quadriceps fibre proportions, in patients.

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