Research

Cigarette smoke attenuates the production of cytokines by human plasmacytoid dendritic cells and enhances the release of IL-8 in response to TLR-9 stimulation

Esmaeil Mortaz^1,2 , Zsofia Lazar³ , Leo Koenderman⁴ , Aletta D Kraneveld¹ , Frans P Nijkamp¹ and Gert Folkerts¹

¹  Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands

²  Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran and Department of Basic Science, Section of Biochemistry, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

³  Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, 78/a Ulloi Str, Budapest, Hungary

⁴  Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, the Netherlands

author email corresponding author email

Respiratory Research 2009, 10:47doi:10.1186/1465-9921-10-47

Published:	10 June 2009

Abstract

Myeloid and plasmacytoid dendritic cells (mDCs, pDC) are crucial to the immune system, detecting microorganisms and linking the innate and adaptive immunity. pDC are present in small quantities in tissues that are in contact with the external environment; mainly the skin, the inner lining of the nose, lungs, stomach and intestines. They produce large amounts of IFN-α after stimulation and are pivotal for the induction of antiviral responses. Chronic obstructive pulmonary disease (COPD) patients are known to be more susceptible to viral infections. We have demonstrated that exposure of mDC to cigarette smoke extract (CSE) leads to the release of chemokines, however, not much is known about the role of pDC in COPD. In this study, we addressed several key questions with respect to the mechanism of action of CSE on human pDC in an in vitro model. Human pDCs were isolated from normal healthy volunteers and subjected to fresh CSE and the levels of IL-8, TNF-α, IP-10, IL-6, IL-1, IL-12 and IL-10 and IFN-α were studied by both ELISA and real time PCR methods. We observed that CSE augmented the production of IL-8 and suppressed the release of TNF-α, IL-6 and IFN-α. Moreover, CSE suppressed PI3K/Akt signalling in pDC. In conclusion, our data indicate that CSE has both the potential to diminish anti-viral immunity by downregulating the release of IFN-α and other pro-inflammatory cytokines while, at the same time, augmenting the pathogenesis of COPD via an IL-8 induced recruitment of neutrophils.