Journal Article

Epigallocatechin-3-Gallate (EGCG), an Active Compound of Green Tea Attenuates Acute Lung Injury Regulating Macrophage Polarization and Krüpple-Like-Factor 4 (KLF4) Expression

Almatroodi, Saleh A., Almatroudi, Ahmad, Alsahli, Mohammed A., Aljasir, Mohammad A., Syed, Mansoor Ali, Rahmani, Arshad Husain

2020

Overview

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are serious clinical complications with a high frequency of morbidity and mortality. The initiation and amplification of inflammation is a well-known aspect in the pathogenesis of ALI and related disorders. Therefore, inhibition of the inflammatory mediators could be an ideal approach to prevent ALI. Epigallocatechin-3-gallate (EGCG), a major constituent of green tea, has been shown to have protective effects on oxidative damage and anti-inflammation. The goal of the present study was to determine whether EGCG improves phenotype and macrophage polarisation in LPS-induced ALI. C57BL/6 mice were given two doses of EGCG (15 mg/kg) intraperitoneally (IP) 1 h before and 3 h after LPS instillation (2 mg/kg). EGCG treatment improved histopathological lesions, Total Leucocyte count (TLC), neutrophils infiltration, wet/dry ratio, total proteins and myeloperoxidase (MPO) activity in LPS-induced lung injury. The results displayed that EGCG reduced LPS-induced ALI as it modulates macrophage polarisation towards M2 status. Furthermore, EGCG also reduced the expression of proinflammatory M1 mediators iNOS TNF-α, IL-1β and IL-6 in the LPS administered lung microenvironment. In addition, it increased the expression of KLF4, Arg1 and ym1, known to augment the M2 phenotype of macrophages. EGCG also alleviated the expression of 8-OHdG, nitrotyrosine, showing its ability to inhibit oxidative damage. TREM1 in the lung tissue and improved lung regenerative capacity by enhancing Ki67, PCNA and Ang-1 protein expression. Together, these results proposed the protective properties of EGCG against LPS-induced ALI in may be attributed to the suppression of M1/M2 macrophages subtype ratio, KLF4 augmentation, lung cell regeneration and regulating oxidative damage in the LPS-induced murine ALI.

• Publisher: MDPI AG,MDPI
• Subject: 8-Hydroxy-2'-Deoxyguanosine - metabolism / acute lung injury / Acute Lung Injury - chemically induced / Acute Lung Injury - drug therapy / Acute Lung Injury - enzymology / Acute Lung Injury - physiopathology / Animals / Anti-Inflammatory Agents - administration & dosage / Anti-Inflammatory Agents - pharmacology / Arginase - metabolism / beta-N-Acetylhexosaminidases - metabolism / Catechin - administration & dosage / Catechin - analogs & derivatives / Catechin - pharmacology / Cell growth / Cell Proliferation - drug effects / Cytokines / Edema / epigallocatechin-3-gallate (EGCG) / Genotype & phenotype / Inflammation / Interleukin-1beta - metabolism / Interleukin-6 - metabolism / Ki-67 Antigen - metabolism / Kruppel-Like Transcription Factors - metabolism / Lectins - metabolism / Lipopolysaccharides - pharmacology / Lungs / macrophage polarisation / Macrophages - metabolism / Mice / Mice, Inbred C57BL / Neutrophils / Nitric Oxide Synthase Type II - genetics / Nitric Oxide Synthase Type II - metabolism / Oxidative stress / Peroxidase - metabolism / Proliferating Cell Nuclear Antigen - metabolism / Protein expression / Proteins / Studies / Tea / Tea - chemistry / Triggering Receptor Expressed on Myeloid Cells-1 - metabolism / Tumor Necrosis Factor-alpha - metabolism / Tyrosine - analogs & derivatives / Tyrosine - metabolism