Ayyanar Sivanantham1, Dhamotharan Pattarayan1, Nandhine Rajasekar1, Adithi Kannan2, Lakshmanan Loganathan3, Ramalingam Bethunaickan4, Santanu Kar Mahapatra2, Rajaguru Palanichamy1, Karthikeyan Muthusamy3, Subbiah Rajasekaran5,6. 1. Department of Biotechnology, BIT-Campus, Anna University, Tiruchirappalli, Tamil Nadu, India. 2. Centre for Research in Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed To Be University, Thanjavur, Tamil Nadu, India. 3. Pharmacogenomics and CADD Lab, Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, India. 4. Department of Immunology, ICMR-National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India. 5. Department of Biotechnology, BIT-Campus, Anna University, Tiruchirappalli, Tamil Nadu, India. rajasekarphd@gmail.com. 6. Department of Biochemistry, ICMR-National Institute for Research in Environmental Health, Kamla Nehru Hospital Building, Gandhi Medical College Campus, Bhopal, Madhya Pradesh, India. rajasekarphd@gmail.com.
Abstract
BACKGROUND: Polarized macrophages induce fibrosis through multiple mechanisms, including a process termed epithelial-to-mesenchymal transition (EMT). Mesenchymal cells contribute to the excessive accumulation of fibrous connective tissues, leading to organ failure. This study was aimed to investigate the effect of tannic acid (TA), a natural dietary polyphenol on M1 macrophage-induced EMT and its underlying mechanisms. MATERIALS: First, we induced M1 polarization in macrophage cell lines (RAW 264.7 and THP-1). Then, the conditioned-medium (CM) from these polarized macrophages was used to induce EMT in the human adenocarcinomic alveolar epithelial (A549) cells. We also analysed the role of TA on macrophage polarization. RESULTS: We found that TA pre-treated CM did not induce EMT in epithelial cells. Further, TA pre-treated CM showed diminished activation of MAPK in epithelial cells. Subsequently, TA was shown to inhibit LPS-induced M1 polarization in macrophages by directly targeting toll-like receptor 4 (TLR4), thereby repressing LPS binding to TLR4/MD2 complex and subsequent signal transduction. CONCLUSION: It was concluded that TA prevented M1 macrophage-induced EMT by suppressing the macrophage polarization possibly through inhibiting the formation of LPS-TLR4/MD2 complex and blockage of subsequent downstream signal activation. Further, our findings may provide beneficial information to develop new therapeutic strategies against chronic inflammatory diseases.
BACKGROUND: Polarized macrophages induce fibrosis through multiple mechanisms, including a process termed epithelial-to-mesenchymal transition (EMT). Mesenchymal cells contribute to the excessive accumulation of fibrous connective tissues, leading to organ failure. This study was aimed to investigate the effect of tannic acid (TA), a natural dietary polyphenol on M1 macrophage-induced EMT and its underlying mechanisms. MATERIALS: First, we induced M1 polarization in macrophage cell lines (RAW 264.7 and THP-1). Then, the conditioned-medium (CM) from these polarized macrophages was used to induce EMT in the humanadenocarcinomic alveolar epithelial (A549) cells. We also analysed the role of TA on macrophage polarization. RESULTS: We found that TA pre-treated CM did not induce EMT in epithelial cells. Further, TA pre-treated CM showed diminished activation of MAPK in epithelial cells. Subsequently, TA was shown to inhibit LPS-induced M1 polarization in macrophages by directly targeting toll-like receptor 4 (TLR4), thereby repressing LPS binding to TLR4/MD2 complex and subsequent signal transduction. CONCLUSION: It was concluded that TA prevented M1 macrophage-induced EMT by suppressing the macrophage polarization possibly through inhibiting the formation of LPS-TLR4/MD2 complex and blockage of subsequent downstream signal activation. Further, our findings may provide beneficial information to develop new therapeutic strategies against chronic inflammatory diseases.
Authors: Cecilia Marmai; Rachel E Sutherland; Kevin K Kim; Gregory M Dolganov; Xiaohui Fang; Sophia S Kim; Shuwei Jiang; Jeffery A Golden; Charles W Hoopes; Michael A Matthay; Harold A Chapman; Paul J Wolters Journal: Am J Physiol Lung Cell Mol Physiol Date: 2011-04-15 Impact factor: 5.464
Authors: Florian Weber; Huy Quang Quach; Mathias Reiersen; Sadaf Yosef Sarraj; Dyala Nidal Bakir; Victor Aleksander Jankowski; Per H Nilsson; Hanna Tiainen Journal: J Biomed Mater Res A Date: 2022-02-26 Impact factor: 4.854