Cigarette smoke enhances {beta}-defensin 2 expression in rat airways via nuclear factor-{kappa}B activation.
β-defensin 2 (BD-2), an antimicrobial peptide, participates in airway defence. Cigarette smoke (CS) is a major risk factor for the development of chronic obstructive pulmonary disease. This study mainly aims to investigate the effect of CS on rat BD-2 (rBD-2) expression in rat airways. Rats were exposed to CS and treated with caffeic acid phenethyl ester (CAPE), a nuclear factor (NF)-κB inhibitor, or astragaloside IV (AS-IV), an active ingredient of Astragalus mongholicus. Besides the analysis of bronchoalveolar lavage fluid (BALF) and histological changes after CS exposure, rBD-2 expression was investigated with immunohistochemistry, reverse transcription PCR and ELISA. Total glutathione and nitric oxide (NO) levels in rat lungs were also detected. CS exposure markedly increased rBD-2 immunoreactivity, as well as rBD-2 mRNA and protein levels in rat airways, which were inhibited by CAPE treatment. Moreover, associated airway inflammation induced by CS was demonstrated by histological changes, increased cell counts and pro-inflammatory cytokines in BALF, and NF-κB activation and high levels of total glutathione and NO, which were all reversed by AS-IV in a dose-dependent fashion. In conclusion, CS exposure induces rBD-2 expression in rat airways via a NF-κB-dependent pathway, and AS-IV attenuates CS-induced airway inflammation due to its anti-inflammatory and antioxidant properties, at least partly through NF-κB inactivation.
Chen
L
L
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan 610041, China.
Sun
B-B
BB
Wang
T
T
Wang
X
X
Li
J-Q
JQ
Wang
H-X
HX
Zhang
S-F
SF
Liu
D-S
DS
Liu
L
L
Xu
D
D
Ou
X-M
XM
Chen
Y-J
YJ
Yang
T
T
Zhou
H
H
Wen
F-Q
FQ
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology; D012907:Smoking / Q000009:adverse effects*; D014132:Trachea / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology; D023083:beta-Defensins / Q000096:biosynthesis*
D016328:NF-kappa B; D012503:Saponins; D014315:Triterpenes; D023083:beta-Defensins; C549474:beta-defensin-2, rat; D009569:Nitric Oxide; C052064:astragaloside A; D005978:Glutathione