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Effects of cigarette smoke on Toll-like receptor ( TLR) activation of chronic obstructive pulmonary disease ( COPD) macrophages.
- Source :
- Clinical & Experimental Immunology; Jun2014, Vol. 176 Issue 3, p461-472, 12p
- Publication Year :
- 2014
-
Abstract
- 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 [ Pam3 CSK4, 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00099104
- Volume :
- 176
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 95702261
- Full Text :
- https://doi.org/10.1111/cei.12289