Ultrasound Combined with Microbubbles Enhances the Effects of Methylprednisolone in Lipopolysaccharide-Induced Human Mesangial Cells

Peng-Fei Sun; Tian Tian; Li-Na Chen; Rong-Guo Fu; Shan-Shan Xu; Hong Ai; Bing Wang; Jian Zhang; Ruo-Yan Si; Zhonglin Chai; Mark E Cooper; Shu-Ting Ren

doi:10.1124/jpet.117.246223

Ultrasound Combined with Microbubbles Enhances the Effects of Methylprednisolone in Lipopolysaccharide-Induced Human Mesangial Cells

J Pharmacol Exp Ther. 2018 Jun;365(3):476-484. doi: 10.1124/jpet.117.246223. Epub 2018 Mar 16.

Authors

Affiliations

¹ Department of Pathology (P.-F.S., T.T., B.W., J.Z., S.-T.R.), Department of Pharmacology (L.-N.C.), and Therapeutic Vaccines Engineering Center of Shaanxi Province (B.W.), School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, People's Republic of China; Department of Pathology, Xi'an City Center Hospital, Xi'an, People's Republic of China (P.-F.S.); Department of Nephrology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China (R.-G.F.); Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, People's Republic of China (S.-S.X.); Department of Ultrasound, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China (H.A.); Shanghai Medical College, Fudan University, Shanghai, People's Republic of China (R.-Y.S.); and Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia (Z.C., M.E.C.).
² Department of Pathology (P.-F.S., T.T., B.W., J.Z., S.-T.R.), Department of Pharmacology (L.-N.C.), and Therapeutic Vaccines Engineering Center of Shaanxi Province (B.W.), School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, People's Republic of China; Department of Pathology, Xi'an City Center Hospital, Xi'an, People's Republic of China (P.-F.S.); Department of Nephrology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China (R.-G.F.); Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, People's Republic of China (S.-S.X.); Department of Ultrasound, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China (H.A.); Shanghai Medical College, Fudan University, Shanghai, People's Republic of China (R.-Y.S.); and Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia (Z.C., M.E.C.) rst@mail.xjtu.edu.cn.

PMID: 29549156
DOI: 10.1124/jpet.117.246223

Abstract

A novel drug delivery system mediated by ultrasound (US) combined with microbubbles (MBs) (US+MB) could improve local drug concentration to enhance its efficacy. To investigate the influence of US+MB on methylprednisolone (MP), the effect of US+MB combined with MP (US+MB+MP) on lipopolysaccharide (LPS)-induced human mesangial cells (HMCs) and the underlying mechanism were explored in this study. The results revealed that HMCs treated with LPS underwent significant proliferation and exhibited an increase in nuclear transcription factor-κB (NF-κB) and transforming growth factor-β1 (TGF-β1) expression and a decrease in cellular apoptosis. This effect was significantly inhibited by MP (30-100 μg/ml), US combined with MBs (3.22 × 10⁷ and 8.05 × 10⁷ bubbles/ml), and US combined with both MBs (1.29 × 10⁷ bubbles/ml) and MP (12 μg/ml) (US+MB1+MP12). The effect of US+MB1+MP12 was better than the effect of 12 μg/ml of MP alone and was similar to the effect of 100 μg/ml of MP. Additionally, the intracellular free MP content was significantly higher in the US+MB1+MP12 group than in the MP12 group. US combined with MBs not only inhibited LPS-induced HMC proliferation and NF-κB and TGF-β1 expression and increased cellular apoptosis but also synergized with the pharmacologic effect of MP. The mechanism is partially due to the US-assisted MB local drug delivery and the anti-inflammatory effect induced by US combined with MBs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects
Cell Line
Cell Proliferation / drug effects
Drug Delivery Systems / methods*
Gene Expression Regulation / drug effects
Humans
Intracellular Space / metabolism
Lipopolysaccharides / pharmacology*
Mesangial Cells / cytology
Mesangial Cells / drug effects*
Mesangial Cells / metabolism
Methylprednisolone / metabolism
Methylprednisolone / pharmacology*
Microbubbles*
NF-kappa B / metabolism
Transforming Growth Factor beta1 / metabolism
Ultrasonic Waves*

Substances

Lipopolysaccharides
NF-kappa B
Transforming Growth Factor beta1
Methylprednisolone