Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Mitigation of monocyte inflammation by inhibition of sodium phosphate co-transporter with phosphonoformic acid and parthenolide in diabetic nephropathy uremia

Wei Yu¹, Ruolan Hu², Yan Zhuo³ , Ya Yang⁴

¹Department of Nephrology, People's Hospital of Chongqing; ²Department of Respiratory, Chongqing Emergency Medical Center, Chongqing, 400014; ³Department of Kidney; ⁴Department of Pharmacy, Southwest Hospital of Third Military Medical University, Chongqing, 400038, China.

For correspondence:- Yan Zhuo Email: yanzhuo2003@163.com

Received: 8 April 2017 Accepted: 24 June 2017 Published: 31 July 2017

Citation: Yu W, Hu R, Zhuo Y, Yang Y. Mitigation of monocyte inflammation by inhibition of sodium phosphate co-transporter with phosphonoformic acid and parthenolide in diabetic nephropathy uremia. Trop J Pharm Res 2017; 16(7):1601-1608 doi: 10.4314/tjpr.v16i7.19

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the effect of sodium phosphate co-transporter (Pit-1) on the regulation of monocyte inflammation in diabetic nephropathy uremia (DNU) patients and the underlying principles of inflammatory immune response during DNU pathogenesis.

Methods: The levels of CD14⁺ CD16⁺ and Pit-1 on peripheral blood mononuclear cells (PBMC) were measured by flow cytometry. Serum C-reactive protein (CRP) and 25(OH)D₃ were detected by immunoturbidimetry while IL-6 and MCP-1 were assayed with enzyme-linked immunoassay (ELISA). The amounts of vitamin D receptors (VDRs) and Pit-1 mRNA in human acute monocytic leukemia cell lines (THP-1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), while western blot was utilized for measurement of NF-κB p65 and p-STAT5.

Results: Compared to the healthy group, DNU patients showed markedly higher CD14⁺CD16⁺, Pit-1, CRP, IL-6 and MCP-1, while 25(OH) D₃ was reduced. Following stimulation with PFA or PTN, comparison with DNU group revealed that THP-1 monocytes showed a significant down-regulation of Pit-1 (1.34 ± 0.06 for PFA; 1.60 ± 0.25 for PTN; p < 0.05); NF-κB p65 (2.65 ± 0.25 for PFA; 3.88 ± 0.13 for PTN; p < 0.01), p-STAT5 (2.49 ± 0.10 for PFA; 3.03 ± 0.09 for PTN; p < 0.01) and a significant decrease in levels of IL-6 (55.38 ± 3.22 for PFA, 68.68 ± 6.01 for PTN; p < 0.05); MCP-1( 39.67 ± 3.62 for PFA; 52.62 ± 5.00 for PTN; p < 0.01), except for VDR (0.64 ± 0.15 for PFA, 0.43 ± 0.03 for PTN; p < 0.05) .

Conclusion: The level of expression of Pit-1 has a positive correlation with the level of inflammatory monocytes, which indicates that Pit-1 can be used as a new biomarker for DNU diagnosis. In addition, since Pit-1 is connected to NF-κB and STAT5 signaling pathways which are critical to inflammatory immune response, development of drugs that target Pit-1 could be an approach in developing new strategies for DNU therapy.

Keywords: Pit-1, Diabetic nephropathy, Uremia, Monocytes, Inflammation, NF-_4;B, STAT5