Tannic acid protects against experimental acute lung injury through downregulation of TLR4 and MAPK |
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Authors: | Ayyanar Sivanantham Dhamotharan Pattarayan Ramalingam Bethunaickan Amrita Kar Santanu Kar Mahapatra Rajesh K. Thimmulappa Rajaguru Palanichamy Subbiah Rajasekaran |
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Affiliation: | 1. Department of Biotechnology, BIT-Campus, Anna University, Tiruchirappalli, India;2. Department of Immunology, National Institute for Research in Tuberculosis, Chennai, India;3. Centre for Research in Infectious Diseases (CRID), School of Chemical & Biotechnology, SASTRA Deemed To Be University, Thanjavur, India;4. Department of Biochemistry, Center of Excellence in Molecular Biology & Regenerative Medicine, 5. JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, India |
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Abstract: | Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) remain a major cause of morbidity and mortality in critically ill patients, and no specific therapies are still available to control the mortality rate. Thus, we explored the preventive and therapeutic effects of tannic acid (TA), a natural polyphenol in the context of ALI. We used in vivo and in vitro models, respectively, using lipopolysaccharide (LPS) to induce ALI in mice and exposing J774 and BEAS-2B cells to LPS. In both preventive and therapeutic approaches, TA attenuated LPS-induced histopathological alterations, lipid peroxidation, lung permeability, infiltration of inflammatory cells, and the expression of proinflammatory mediators. In addition, in-vitro study showed that TA treatment could reduce the expression of proinflammatory mediators. Further studies revealed that TA-dampened inflammatory responses by downregulating the LPS-induced toll-like receptor 4 (TLR4) expression and inhibiting extracellular-signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) activation. Furthermore, cells treated with the inhibitors of ERK1/2 (PD98059) and p38 (SB203580) mitigated the expression of cytokines induced by LPS, thus suggesting that ERK1/2 and p38 activity are required for the inflammatory response. In conclusion, TA could attenuate LPS-induced inflammation and may be a potential therapeutic agent for ALI-associated inflammation in clinical settings. |
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Keywords: | ALI cytokines LPS MAPK tannic acid TLR4 |
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