Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway.

Inflammation is an important cause of chronic obstructive pulmonary disease (COPD) and its acute exacerbation. However, the critical role of C-C chemokine receptor (CCR)1 in progression of cigarette smoke-induced chronic inflammation remains unclear. We studied CCR1 expression using immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction (RT-PCR) in COPD patients and controls. Cytokine levels in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). In vitro, we investigated Janus kinase/signal transducers and activators of transcription (JAK/STAT)/nuclear factor-κB (NF-κB) signaling in cigarette smoke extract-induced or CCR1 deficiency/overexpressed mouse macrophage cell line MH-S by RT-PCR and western blot, and measured the cytokine levels in the supernatant with ELISA. We found that CCR1 expression was upregulated in COPD patients and there was a negative correlation between CCR1 levels and predicted % forced expiratory volume in 1 min. Inflammatory cytokine levels in the peripheral blood were higher in COPD patients than controls, and these were positively correlated with CCR1 levels. CCR1 was shown to play a critical role in regulating smoke-induced inflammation via JAK/STAT3/NF-κB signaling in vitro. CCR1 may play a critical role in airway inflammation in COPD. Additionally, understanding the molecular mechanism may help develop novel methods for the treatment of COPD.