Ann Lab Med 2020; 40(5): 390-397  https://doi.org/10.3343/alm.2020.40.5.390
Cytokines, Angiogenesis, and Extracellular Matrix Degradation are Augmented by Oxidative Stress in Endometriosis
Amalesh Nanda, M.Pharm.1, Thangapandi K., M.Sc.1, Priyanka Banerjee, Ph.D.2, Mainak Dutta, Ph.D.3, Tsering Wangdi, M.D.4, Pramod Sharma, M.D.4, Koel Chaudhury, Ph.D.2, and Saikat Kumar Jana, Ph.D.1
1Department of Biotechnology, National Institute of Technology, Yupia, Papum Pare, Arunachal Pradesh, India; 2School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal, India; 3Department of Biotechnology, Birla Institute of Technology and Science, Pilani, Dubai Campus, Dubai International Academic City, Dubai, UAE; 4Department of Obstetrics and Gynecology, Pratiksha Hospital, Borbari, Guwahati, Assam, India
Corresponding author: Saikat Kumar Jana, Ph.D.
Department of Biotechnology, National Institute of Technology, Yupia, District: Papum Pare, Arunachal Pradesh-791112, India
Tel: +91-9485230608
Fax: +91-360-2284972
E-mail: saikatmicro4@gmail.com
Received: September 17, 2019; Revised: January 26, 2020; Accepted: April 1, 2020; Published online: September 1, 2020.
© Korean Society for Laboratory Medicine. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: The effect of the interplay among inflammation, angiogenesis, extracellular matrix (ECM) degradation, and oxidative stress (OS) on the pathogenesis of endometriosis remains unclear. Previously, we demonstrated the role of OS in endometriosis. Here, we performed a comprehensive investigation of several molecules involved in inflammation, angiogenesis, and ECM degradation in women with endometriosis to study their interplay with OS.
Methods: Blood samples were collected from women with endometriosis (N=80), as well as from women with tubal factor infertility as controls (N=80). Interleukin (IL)-1β, tumor necrosis factor-alpha, interferon-gamma, transforming growth factor-beta, IL-4, -10, -2, -6, -8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, -9, tissue inhibitor of metalloproteinases (TIMP)-1, -2, and cyclooxygenase (COX)-2 levels in serum samples were measured using an ELISA. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in peripheral blood mononuclear cells was measured using flow cytometry.
Results: Cytokines, VEGF, MMPs, and COX-2 were significantly higher and TIMPs were significantly lower in patients with endometriosis. Multivariate statistical analysis indicated that IL-10 was the most significant variable capable of discriminating endometriosis samples from controls.
Conclusions: Deregulation of NF-κB activation by OS affects the expression of various cytokines in endometriosis. Elevated cytokine levels further up-regulate IL-10, which subsequently activates the MMPs, leading to excessive ECM degradation and angiogenesis. Moreover, IL-10 emerged as the most important molecule involved in the pathogenesis of endometriosis. Measurement of these molecules may help in better management of the patients with endometriosis.
Keywords: Oxidative stress (OS), Endometriosis, Extracellular matrix, Cytokines



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