Cytokines, Angiogenesis, and Extracellular Matrix Degradation are Augmented by Oxidative Stress in Endometriosis
Nanda Amalesh, Thangapandi K., Banerjee Priyanka, Dutta Mainak, Wangdi Tsering, Sharma Pramod, Chaudhury Koel, Jana Saikat Kumar,
소속 상세정보
( Nanda Amalesh )
National Institute of Technology Department of Biotechnology
( Thangapandi K. )
National Institute of Technology Department of Biotechnology
( Banerjee Priyanka )
Indian Institute of Technology Kharagpur School of Medical Science and Technology
( Dutta Mainak )
Birla Institute of Technology and Science Department of Biotechnology
( Wangdi Tsering )
Pratiksha Hospital Department of Obstetrics and Gynecology
( Sharma Pramod )
Pratiksha Hospital Department of Obstetrics and Gynecology
( Chaudhury Koel )
Indian Institute of Technology Kharagpur School of Medical Science and Technology
( Jana Saikat Kumar )
National Institute of Technology Department of Biotechnology
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.
키워드
Oxidative stress (OS); Endometriosis; Extracellular matrix; Cytokines
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