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03-06-2010 | Respiratory | Article

PI3Kδ expression, signaling increased in lung macrophages of COPD patients


Free abstract

MedWire News: Research suggests that impaired glucocorticoid function in the lungs of patients with chronic obstructive pulmonary disease (COPD) might be caused by increased phosphoinositol 3–kinase (PI3K)δ expression and signaling.

"Selective inhibition of PI3Kδ might restore glucocorticoid function in patients with COPD and might therefore present a potential therapeutic target," write John Marwick (University of Edinburgh, UK) and colleagues in the Journal of Allergy and Clinical Immunology.

In COPD and asthma, the use of glucocorticoid therapy does not always suppress chronic inflammation, possibly because of increases in oxidative stress.

The PI3K family is involved in numerous cellular functions, but the PI3Kδ and PI3Kγ isoforms are expressed in leukocytes and play a central role in inflammatory cell function. One study in mice recently showed that a reduction in the oxidant-mediated glucocorticoid function is prevented by the inhibition of PI3Kδ function.

With this in mind, Marwick and colleagues assessed whether PI3Kδ played a role in the reduction of glucocorticoid responsiveness in COPD patients.

Peripheral lung tissue was taken from 24 individuals with COPD, 20 age-matched smokers with normal lung function, and 13 healthy nonsmokers.

PI3Kδ and Akt phosphorylation were significantly increased in the macrophages of patients with COPD when compared with smoking and nonsmoking controls.

Oxidative stress, induced in vitro, also resulted in the phosphorylation of Akt in monocytes and macrophages, but this was stopped when PI3Kδ was selectively inhibited.

The inhibition of PI3Kγ did not have an effect on the phosphorylation of Akt.

"An increase in PI3Kδ activation might therefore represent a mechanism of glucocorticoid insensitivity in patients with COPD," conclude Marwick and colleagues.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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