Tanshinone ⅡA ameliorates acute lung injury by inhibition of the NLRP3 inflammasome
Keywords:tanshinone IIA, acute lung injury, inflammation, NLRP3, inflammasome
- The Nucleotide-binding oligomerization domain (NOD)-like receptor family protein 3 (NLRP3) inflammasome plays an essential role in acute lung injury (ALI). The protective effect of tanshinone IIA on ALI has been verified in several animal models.
- Tanshinone IIA significantly ameliorated oleic acid-induced pulmonary histological pathology, edema, impaired gas exchange, increased levels of cytokines in rats, and attenuated increased protein levels of NLRP3, caspase-1 and interleukin-1β in pulmonary tissues.
- Our results extend the knowledge of the protective effect of tanshinone IIA, a potential new tool for ALI treatment.
Abstract: Tanshinone IIA is the phenanthrenequinone derivative extracted from the perennial plant Salvia miltiorrhiza Bunge (red sage). We investigated whether inhibition of the nucleotide-binding oligomerization domain (NOD)-like receptor family protein 3 (NLRP3) inflammasome mediates the protective effect of tanshinone IIA in acute lung injury (ALI) induced in rats by oleic acid (OA) injection. Compared with the control treatment, OA injection induced pulmonary histological impairment, increased the lung wet/dry weight ratio (7.0±1.1 vs 4.3±0.6 ) and CO2 partial pressure (PaCO2) (52±6.4 vs 40±3.6 mmHg), decreased arterial O2 partial pressure (PaO2) (63±8.4 vs 100±3.0 mmHg), and increased tumor necrosis factor α (TNFα) (8.8±2.3 vs 5.2±1.5 pg/mL), monocyte chemoattractant protein-1 (MCP-1) (36.1±4.9 vs 25.2±6.6 pg/mL) and interleukin-1β (IL-1β) (15.9±3.2 vs 4.6±1.3 pg/mL) in the bronchoalveolar lavage (BAL) fluid. Tanshinone IIA provided protection against ALI, observed as a reduction in the lung wet/dry weight ratio and CO2 partial pressure, and increased O2 partial pressure. The cytokine increase was also prevented. Tanshinone IIA attenuated increased protein levels of NLRP3, caspase-1 and IL-1β in pulmonary tissues, suggesting that it ameliorates ALI by preventing NLRP3 inflammasome activation.
Received: December 7, 2018; Revised: January 25, 2019; Accepted: January 26, 2019; Published online: March 18, 2019
How to cite this article: Chen T, Qin S, Dai Y. Tanshinone IIA ameliorates acute lung injury by inhibition of the NLRP3 inflammasome. Arch Biol Sci. 2019;71(2):315-20.
Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353:1685-93.
Bhattacharya J, Matthay MA. Regulation and Repair of the Alveolar-Capillary Barrier in Acute Lung Injury. Annu Rev Physiol. 2013;75:593-615.
Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016;315:788-800.
Malhotra A. Low-tidal-volume ventilation in the acute respiratory distress syndrome. N Engl J Med. 2007;357:1113-20.
Ware LB. Pathophysiology of acute lung injury and the acute respiratory distress syndrome. Semin Respir Crit Care Med. 2006;27:337-49.
Ganter MT, Roux J, Miyazawa B, Howard M, Frank JA, Su G, Sheppard D, Violette SM, Weinreb PH, Horan GS, Matthay MA, Pittet JF. Interleukin-1β causes acute lung injury via αvβ5 and αvβ6 integrin-dependent mechanisms. Circ Res. 2008;102:804-12.
Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002;10:417-26.
Gross O, Thomas CJ, Guarda G, Tschopp J. The inflammasome: an integrated view. Immunol Rev. 2011;243:136-51.
Schenten D, Medzhitov R. The control of adaptive immune responses by the innate immune system. Adv Immunol. 2011;109:87-124.
Hosseinian N, Cho Y, Lockey RF, Kolliputi N. The role of the NLRP3 inflammasome in pulmonary diseases. Ther Adv Respir Dis. 2015;9:188-97.
Grailer JJ, Canning BA, Kalbitz M, Haggadone MD, Dhond RM, Andjelkovic AV, Zetoune FS, Ward PA. Critical role for the NLRP3 inflammasome during acute lung injury. J Immunol. 2014;192:5974-83.
Jones HD, Crother TR, Gonzalez-Villalobos RA, Jupelli M, Chen S, Dagvadorj J, Arditi M, Shimada K. The NLRP3 inflammasome is required for the development of hypoxemia in LPS/mechanical ventilation acute lung injury. Am J Respir Cell Mol Biol. 2014;50:270-80.
Liu Z, Zhao H, Liu W, Li T, Wang Y, Zhao M. NLRP3 inflammasome activation is essential for paraquat-induced acute lung injury. Inflammation. 2015;38:433-44.
Han S, Cai W, Yang X, Jia Y, Zheng Z, Wang H, Li J, Li Y, Gao J, Fan L, Hu D. ROS-Mediated NLRP3 Inflammasome Activity Is Essential for Burn-Induced Acute Lung Injury. Mediators Inflamm. 2015;2015:720457.
Liu T, Zhou Y, Li P, Duan JX, Liu YP, Sun GY, Wan L, Dong L, Fang X, Jiang JX, Guan CX. Blocking triggering receptor expressed on myeloid cells-1 attenuates lipopolysaccharide-induced acute lung injury via inhibiting NLRP3 inflammasome activation. Sci Rep. 2016;6:39473.
Zhang Y, Li X, Grailer JJ, Wang N, Wang M, Yao J, Zhong R, Gao GF, Ward PA, Tan DX, Li X. Melatonin alleviates acute lung injury through inhibiting the NLRP3 inflammasome. J Pineal Res. 2016;60:405-14.
Shi XM, Huang L, Xiong SD, Zhong XY. Protective effect of tanshinone II A on lipopolysaccharide-induced lung injury in rats. Chin J Integr Med. 2007;13:137-40.
Xu M, Dong MQ, Cao FL, Liu ML, Wang YX, Dong HY, Huang YF, Liu Y, Wang XB, Zhang B, Zhao PT, Luo Y, Niu W, Cui Y, Li ZC. Tanshinone IIA reduces lethality and acute lung injury in LPS-treated mice by inhibition of PLA2 activity. Eur J Pharmacol. 2009;607:194-200.
Xu M, Cao F, Liu L, Zhang B, Wang Y, Dong H, Cui Y, Dong M, Xu D, Liu Y, Zhao P, Niu W, Li Z. Tanshinone IIA-induced attenuation of lung injury in endotoxemic mice is associated with reduction of hypoxia-inducible factor 1α expression. Am J Respir Cell Mol Biol. 2011;45:1028-35.
Xu M, Cao FL, Zhang YF, Shan L, Jiang XL, An XJ, Xu W, Liu XZ, Wang XY. Tanshinone IIA therapeutically reduces LPS-induced acute lung injury by inhibiting inflammation and apoptosis in mice. Acta Pharmacol Sin. 2015;36:179-87.
Li J, Xu M, Fan Q, Xie X, Zhang Y, Mu D, Zhao P, Zhang B, Cao F, Wang Y, Jin F, Li Z. Tanshinone IIA ameliorates seawater exposure-induced lung injury by inhibiting aquaporins (AQP) 1 and AQP5 expression in lung. Respir Physiol Neurobiol. 2011;176:39-49.
Li JH, Xu M, Xie XY, Fan QX, Mu DG, Zhang Y, Cao FL, Wang YX, Zhao PT, Zhang B, Jin FG, Li ZC. Tanshinone IIA suppresses lung injury and apoptosis, and modulates protein kinase B and extracellular signal-regulated protein kinase pathways in rats challenged with seawater exposure. Clin Exp Pharmacol Physiol. 2011;38:269-77.
Wang Y, Wu H, Niu W, Chen J, Liu M, Sun X, Li Z. Tanshinone IIA attenuates paraquat‑induced acute lung injury by modulating angiotensin‑converting enzyme 2/angiotensin‑(1‑7) in rats. Mol Med Rep. 2018;18:2955-62.
Hu Q, Wei B, Wei L, Hua K, Yu X, Li H, Ji H. Sodium tanshinone IIA sulfonate ameliorates ischemia-induced myocardial inflammation and lipid accumulation in Beagle dogs through NLRP3 inflammasome. Int J Cardiol. 2015;196:183-92.
Yoshii C,NagataN, TaoY, Suematsu R,NikaidoY,KidoM. Relationship between inflammatory cells in bronchoalveolar lavage fluid and pathologic changes in the lung interstitium. Respiration 1998;65:386–92.