Effect of JQ-1 on monocyte-derived macrophage (MDM) phagocytosis of bacteria and cytokine release

Rationale: A characteristic of COPD is bacterial colonisation in the lower airway, possibly due to defective macrophage phagocytosis. This is associated with macrophage activation and increased cytokine release. JQ-1, a bromodomain inhibitor, down-regulates inflammatory protein transcription and may be anti-inflammatory. However, it may have other effects. This study compares the effect of JQ-1, on phagocytosis of bacteria in an MDM model using cells cultured from non-smokers, smokers and COPD subjects. Methods: Human monocyte-derived macrophages (MDMs) cultured (12 days + GMCSF) from non-smokers, smokers and COPD subjects were pre-treated with JQ-1 (1x10 -12 - 1x10 -5 M) for 4 or 24hrs. Phagocytosis of labelled H. Influenzae (HI) and S. Pneumoniae (SP) was measured by Fluorimetry. Cytokines TNF-α and CXCL-8 were measured by ELISA. Results: JQ-1 did not attenuate HI and SP stimulated release of CXCL-8 or TNF-α at 4 or 24hrs. MDM survival + JQ-1 (1μM): 4h = 156% and 24hr = 85% (relative to bacteria treated MDMs = 100%) Conclusions: JQ-1 had no effect on phagocytosis until high concentration (1μM). However, JQ-1 did not suppress CXCL-8 or TNF-.α release in this model. MDMs may not be a good model for study of bromodomain inhibitor effects and investigation of JQ-1 effects in other macrophage phenotypes is required.