Increased expression of phosphodiesterase 4 (PDE4) A, B and D in alveolar macrophages from chronic obstructive pulmonary disease (COPD) patients

Simon Lea, Aleksandra Metryka, Fabrizio Facchinetti, Dave Singh

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Phosphodiesterase-4 (PDE4) inhibitors, such as roflumilast, may offer novel anti-inflammatory strategies in respiratory diseases, including chronic obstructive pulmonary disease (COPD). Although it is widely accepted that PDE4 is expressed in macrophages, there is a lack of knowledge regarding the expression levels of PDE4 subtypes in alveolar macrophages (AM) from COPD patients. We examined the mRNA levels of PDE4 A, B and D in AM from patients with COPD and the modulatory effects of roflumilast on LPS-evoked cytokine release. Methods: mRNA levels of PDE4 A, B and D were analysed in AM from 11 COPD patients, 8 smokers and 8 non-smokers by real-time PCR. AM from 11 COPD patients were stimulated with LPS following preincubation with roflumilast. After 24h, the supernatants were analysed for TNFα, IL-8 and IL-6. Results: Expression of PDE4, A, B and D, are significantly augmented in AM form COPD patients compared to non-smoking controls (P<0.05). Roflumilast significantly (P<0.01) reduced LPS induced TNFα production in a concentration-dependent fashion (0.05-5μM) while had no significant effect on IL-6 or IL-8 release Conclusion: mRNA levels of PDE4 A, B and D are increased in AM from COPD patients. Roflumilast inhibits TNFα production from AM from COPD patients
Original languageEnglish
JournalThe European respiratory journal
Volume38
Publication statusPublished - 1 Sept 2011

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