Inhibition of VEGF and MMP-9 production by Pregabalin in human immunocompetent cells in vitro

Fatemeh Hajighasemi | Leila Darouni

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URL :   http://research.shahed.ac.ir/WSR/WebPages/Report/PaperView.aspx?PaperID=148173
Date :  2020/09/04
Publish in :     (European Respiratory Society Annual Congress 2020 (ERS 2020

Link :  http://erscongress.org/
Keywords :immunocompetent , Pregabalin , MMP, VEGF

Abstract :

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Introduction: Pregabalin, a neuromodulator, has been used for treatment of some neurologic disorders such as fibromyalgia, anxiety and neuropathic pains. Anti-neuroinflammatory effects of pregabalin have also been shown. Vascular endothelial growth factor (VEGF)(a cytokine) and Matrix metalloproteinases (MMPs)(a family of proteases degrade extracellular matrix), have an important role in inflammation. Higher levels of VEGF and MMP-9 in airway inflammation, chronic obstructive pulmonary disease (COPD) and asthma exacerbation and a correlation between MMP-9 and VEGF levels in some lung diseases has been found. Objectives: In this study effect of pregabalin on VEGF and MMP-9 production in human leukemic monocytes (U937) and T cells (Molt-4) has been assessed in vitro. Methods: U937 and Molt-4 cells were cultured in RPMI 1640 complete medium. Cells at logarhytmic growth phase were stimulated by optimal concentration of phorbol 12-myristate 13-acetate (PMA) and next treated with different doses of pregabalin (1-100 μg/ml) for 24 hours. MMP-9 and VEGF concentrations in culture supernates were measured by ELISA. Results: Pregabalin significantly reduced MMP-9 and VEGF production in PMA-stimulated U937 and Molt-4 cells dose-dependently. Conclusion: Pregabalin down-regulates VEGF and MMP-9 in U937 and Molt-4 cells. As VEGF and MMP-9 have an important role in inflammation, anti-inflammatory properties of pregabalin may be partly due to its inhibitory effects on MMP-9/VEGF expression. So pregabalin along with its positive effects in neuropathic disorders can be useful in planning of therapeutic ways for airway inflammatory diseases such as COPD in which VEGF and MMP-9 are highly-expressed.

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