You are here: Home Published Research Effects of cigarette smoke on Toll-like receptor (TLR) activation of chronic obstructive pulmonary disease (COPD) macrophages.

H. J Metcalfe, S. Lea, D. Hughes, R. Khalaf, K. Abbott-Banner, and D. Singh (2014)

Effects of cigarette smoke on Toll-like receptor (TLR) activation of chronic obstructive pulmonary disease (COPD) macrophages.

Clinical and experimental immunology, 176(3):461–472.

Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal innate immune response. We have investigated the changes in the innate immune response of COPD alveolar macrophages exposed to both cigarette smoke and Toll-like receptor (TLR) stimulation. COPD and control alveolar macrophages were exposed to cigarette smoke extract (CSE) followed by TLR-2, -4 and -5 ligands [Pam3CSK4, lipopolysaccharide (LPS) and phase I flagellin (FliC), respectively] or non-typeable Haemophilus influenzae (NTHi). CSE exposure suppressed TLR-induced tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and regulated on activation, normal T cell expressed and secreted (RANTES) production in both COPD and control alveolar macrophages, but had no effect on interleukin 8 (CXCL8) production. Similarly, CSE suppressed NTHi-induced TNF-α but not NTHi-induced CXCL8 production in COPD alveolar macrophages. Gene expression analysis showed that CSE suppressed LPS-induced TNF-α transcription but not CXCL8 transcription in COPD alveolar macrophages. The dampening effect of CSE on LPS-induced cytokine production was associated with a reduction in p38, extracellular signal regulated kinase (ERK) and p65 activation. In conclusion, CSE caused a reduced innate immune response in COPD alveolar macrophages, with the exception of persistent CXCL8 production. This could be a mechanism by which alveolar macrophages promote neutrophil chemotaxis under conditions of oxidative stress and bacterial exposure.

Aged, Aged, 80 and over, Case-Control Studies, Cytokines, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Female, Gene Expression, Gene Expression Regulation, Haemophilus Infections, Humans, Interleukin-8, Macrophage Activation, Macrophages, Macrophages, Alveolar, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Smoking, Toll-Like Receptors, Transcription Factor RelA, Tumor Necrosis Factor-alpha, p38 Mitogen-Activated Protein Kinases
Aged, Aged, 80 and over, Case-Control Studies, Cytokines, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Female, Gene Expression, Gene Expression Regulation, Haemophilus Infections, Humans, Interleukin-8, Macrophage Activation, Macrophages, Macrophages, Alveolar, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Smoking, Toll-Like Receptors, Transcription Factor RelA, Tumor Necrosis Factor-alpha, p38 Mitogen-Activated Protein Kinases
 
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