PT  - JOURNAL ARTICLE
AU  - Akira Koarai
AU  - Satoru Yanagisawa
AU  - Hisatoshi Sugiura
AU  - Tomohiro Ichikawa
AU  - Keiichiro Akamatsu
AU  - Tsunahiko Hirano
AU  - Masanori Nakanishi
AU  - Kazuto Matsunaga
AU  - Yoshiaki Minakata
AU  - Masakazu Ichinose
TI  - Cigarette smoking augments toll-like receptor 3 expression and responses in macrophages
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - 218
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/218.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/218.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Toll-like receptor 3 (TLR3), which reacts to viral-derived double-stranded RNA, is suggested to be involved in the immune responses during viral infection. However, the role of TLR3-mediated response in the pathophysiology of chronic obstructive pulmonary disease (COPD) is unclear.The expression of TLR3 in alveolar macrophages in human lung tissues was analyzed by immunohistochemistry. Furthermore, the effect of cigarette smoke on the expression and responses of TLR3 in macrophage lineage cells was examined.TLR3-positive alveolar macrophages were significantly increased in smokers and COPD subjects compared with non-smoker control subjects, but there was no difference between smokers and COPD subjects. The values of TLR3-positive macrophages were positively correlated with the smoking history and negatively correlated with the values of corrected carbon monoxide diffusing capacity by alveolar ventilation (DLCO/VA) (p &amp;lt; 0.001, rs = -0.56), but not with the values of forced expiratory volume in 1 second (FEV1)% of predicted. Furthermore, cigarette smoke extract potentiated the expression of TLR3 in monocyte-derived macrophages and significantly augmented the release of interleukin-8 (CXCL8) and total matrix metalloprotease-9 activity in TLR3 ligand-treated cells.These data suggest that cigarette smoking potentiates the expression and responses of TLR3 in alveolar macrophages, which might affect the pathogenesis of COPD as well as its exacerbation.