PMID- 29549156 OWN - NLM STAT- MEDLINE DCOM- 20191014 LR - 20191014 IS - 1521-0103 (Electronic) IS - 0022-3565 (Linking) VI - 365 IP - 3 DP - 2018 Jun TI - Ultrasound Combined with Microbubbles Enhances the Effects of Methylprednisolone in Lipopolysaccharide-Induced Human Mesangial Cells. PG - 476-484 LID - 10.1124/jpet.117.246223 [doi] AB - 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-kappaB (NF-kappaB) and transforming growth factor-beta1 (TGF-beta1) expression and a decrease in cellular apoptosis. This effect was significantly inhibited by MP (30-100 mug/ml), US combined with MBs (3.22 x 10(7) and 8.05 x 10(7) bubbles/ml), and US combined with both MBs (1.29 x 10(7) bubbles/ml) and MP (12 mug/ml) (US+MB1+MP12). The effect of US+MB1+MP12 was better than the effect of 12 mug/ml of MP alone and was similar to the effect of 100 mug/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-kappaB and TGF-beta1 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. CI - Copyright (c) 2018 by The American Society for Pharmacology and Experimental Therapeutics. FAU - Sun, Peng-Fei AU - Sun PF AD - 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.). FAU - Tian, Tian AU - Tian T AD - 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.). FAU - Chen, Li-Na AU - Chen LN AD - 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.). FAU - Fu, Rong-Guo AU - Fu RG AD - 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.). FAU - Xu, Shan-Shan AU - Xu SS AD - 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.). FAU - Ai, Hong AU - Ai H AD - 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.). FAU - Wang, Bing AU - Wang B AD - 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.). FAU - Zhang, Jian AU - Zhang J AD - 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.). FAU - Si, Ruo-Yan AU - Si RY AD - 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.). FAU - Chai, Zhonglin AU - Chai Z AD - 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.). FAU - Cooper, Mark E AU - Cooper ME AD - 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.). FAU - Ren, Shu-Ting AU - Ren ST AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180316 PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Transforming Growth Factor beta1) RN - X4W7ZR7023 (Methylprednisolone) SB - IM MH - Apoptosis/drug effects MH - Cell Line MH - Cell Proliferation/drug effects MH - Drug Delivery Systems/*methods MH - Gene Expression Regulation/drug effects MH - Humans MH - Intracellular Space/metabolism MH - Lipopolysaccharides/*pharmacology MH - Mesangial Cells/cytology/*drug effects/metabolism MH - Methylprednisolone/metabolism/*pharmacology MH - *Microbubbles MH - NF-kappa B/metabolism MH - Transforming Growth Factor beta1/metabolism MH - *Ultrasonic Waves EDAT- 2018/03/20 06:00 MHDA- 2019/10/15 06:00 CRDT- 2018/03/18 06:00 PHST- 2017/11/07 00:00 [received] PHST- 2018/03/09 00:00 [accepted] PHST- 2018/03/20 06:00 [pubmed] PHST- 2019/10/15 06:00 [medline] PHST- 2018/03/18 06:00 [entrez] AID - jpet.117.246223 [pii] AID - 10.1124/jpet.117.246223 [doi] PST - ppublish SO - J Pharmacol Exp Ther. 2018 Jun;365(3):476-484. doi: 10.1124/jpet.117.246223. Epub 2018 Mar 16.