Inhibitory effects of casticin on migration of eosinophil and expression of chemokines and adhesion molecules in A549 lung epithelial cells via NF-κB inactivation.
BACKGROUND
The fruits of Vitex rotundifolia L. have long been used for the treatment of inflammation of the respiratory tract in East Asia.


OBJECTIVE
To determine if casticin, one of the constituents of Vitex rotundifolia L., has anti-allergic and anti-inflammatory effects in asthma.


METHODS
The in vitro anti-inflammatory activity of casticin was studied in A549 human type II-like epithelial lung cells using an eotaxin inhibition assay. Additionally, its effects on eotaxin, regulated on activation normal T cell expressed and secreted (RANTES), vascular cell adhesion molecule (VCAM)-1, and inter-cellular adhesion molecule (ICAM)-1 expression were investigated by real time-polymerase chain reaction (real time-PCR). The inhibition of nuclear factor κB (NF-κB) activity in the presence of casticin was determined by analyzing confocal microscopy images of fluorescence immunocytochemical analysis while the suppression of inhibitory κB (IκB)-α phosphorylation was studied using Western blot analysis. Finally, the inhibitory effect of casticin on eosinophil migration toward prestimulated A549 cell media was measured using the human eosinophilic leukemia cell line.


CONCLUSIONS
Casticin significantly suppressed eotaxin production in cytokine activated A549 lung epithelial cells. Casticin also suppressed the mRNA expression levels of eotaxin, RANTES, VCAM-1, and ICAM-1, which subsequently contributed to the inhibition of eosinophil migration. Furthermore, casticin inhibited IκB-α phosphorylation and nuclear translocation of p65 in A549 cells.


CONCLUSIONS
Casiticin inhibited the eosinophil migration and activity of chemokines and adhesion molecules involved in the inflammatory process of asthma by suppressing the NF-κB pathway. These results suggest that casticin has the potential for use in the treatment of allergic asthma.
Department of Physiology, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
Duck-jae
DJ
Koh
Hong-sik
HS
Ahn
Hwan-Suck
HS
Chung
Hyojung
H
Lee
Youngchul
Y
Kim
Jin-yong
JY
Lee
Deog-gon
DG
Kim
Moochang
M
Hong
Minkyu
M
Shin
Hyunsu
H
Bae
D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D005638:Fruit; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D020950:Vitex / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D019742:Chemokines, CC; D016207:Cytokines; D005419:Flavonoids; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010936:Plant Extracts; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; C054133:casticin