Novel approach to study the cardiovascular effects and mechanism of action of urban particulate matter using lung epithelial-endothelial tetra-culture system.
In vitro models have become increasingly sophisticated, and their usefulness in supporting toxicity testing is well established. The present study was designed to establish a novel in vitro model that mimics the cellular network surrounding airways and pulmonary blood vessels, to study the cardiovascular toxic effects of particulate matter (PM). Transwell culture method was used to develop a novel tetra-culture system consisting of tri-cultures (one lung epithelial and two immune cell lines) in the apical chamber and endothelial cells in the basolateral chamber. Tri-cultures were exposed to standard reference material (SRM) 1648a, an urban PM. SRM 1648a did not show cytotoxic effects; however, it increased IL-6 level in apical and basolateral chambers. The cells in the basolateral chamber showed increased monocyte adhesion. Furthermore, exposure of tri-cultured cells to SRM 1648a in the apical chamber induced ICAM-1 expression in endothelial cells in the basolateral chamber by activating the IL-6/STAT3 pathway. In conclusion, a tetra-culture system was established to facilitate the identification of cellular adhesion molecule expression induced by the interaction between pulmonary epithelial and endothelial cells. The tetra-culture system will contribute to elucidation of the relationships between inhalable PM and cardiovascular diseases.
School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 16419, Republic of Korea; Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan.
Ha Ryong
HR
Kim
School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 16419, Republic of Korea.
Han Soo
HS
Cho
School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 16419, Republic of Korea.
Da Young
DY
Shin
School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 16419, Republic of Korea. Electronic address: khchung@skku.edu.
Kyu Hyuck
KH
Chung
D000393:Air Pollutants / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002947:Cities; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D052638:Particulate Matter / Q000633:toxicity*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000393:Air Pollutants; C508600:IL6 protein, human; D015850:Interleukin-6; D052638:Particulate Matter; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1
Cardiovascular disease; Cell adhesion molecule; Tetra-culture system; Urban particulate matter