Tannic acid protects against experimental acute lung injury through downregulation of TLR4 and MAPK

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, invitro 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. K E Y W O R D SALI, cytokines, LPS, MAPK, tannic acid, TLR4

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

“…Tannic acid pre‐ and post‐treatments markedly attenuated lung injury, lung inflammatory condition, inflammatory cell infiltration and inflammatory mediator expression (TNF‐α, IFN‐γ, IL‐1β, IL‐6, MCP‐1 and MIP‐1α) in LPS-induced ALI mice. In addition, tannic acid significantly attenuated inflammatory responses in J774 and BEAS-2B cells stimulated by LPS, possibly due to down-regulation of the TLR4 and MAPK signaling pathways [ 325 ].…”

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

“…In this regard, evaluating the role played by TLR4 signaling in the lungs is critical to improving the outcomes in COVID-19 patients. In the LPS-induced acute lung injury murine model of sepsis, inhibition of TLR4 signaling using monoclonal antibodies [ 58 ], pharmacological intervention [ [59] , [60] , [61] ] as well as miRNA-based treatments [ 62 ] could be beneficial for these patients.…”

Negative Effects of SIGIRR on TRAF6 Ubiquitination in Acute Lung Injury In Vitro

“…Currently, there are no specific therapies for ALI/ARDS [ 7 ]. TLRs are important pathogen pattern recognition receptors in the innate immune system [ 10 ]. The immune response combined with TLR-4 could induce the TRAF6-TRIF-binding process and NF- κ B activation [ 33 ].…”