Anti‑inflammatory effects of triptolide by inhibiting the NF‑κB signalling pathway in LPS‑induced acute lung injury 
in a murine model

Wang,Xian; Zhang,Lei; Duan,Wei; Liu,Bin; Gong,Ping; Ding,Yusong; Wu,Xiongwen

doi:10.3892/mmr.2014.2191

Anti‑inflammatory effects of triptolide by inhibiting the NF‑κB signalling pathway in LPS‑induced acute lung injury in a murine model

Authors:
- Xian Wang
- Lei Zhang
- Wei Duan
- Bin Liu
- Ping Gong
- Yusong Ding
- Xiongwen Wu
View Affiliations

Affiliations: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China, Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Shihezi University, Shihezi, Xinjiang 832000, P.R. China, Department of Emergency, The First Affiliated Hospital, College of Medicine, Shihezi University, Shihezi, Xinjiang 832000, P.R. China, Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Shihezi University, Shihezi, Xinjiang 832000, P.R. China, Department of Public Health, College of Medicine, Shihezi University, Shihezi, Xinjiang 832000, P.R. China
Published online on: April 28, 2014 https://doi.org/10.3892/mmr.2014.2191
Pages: 447-452

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Triptolide is one of the main active components in the Chinese herb Tripterygium wilfordii Hook F, which has been demonstrated to possess anti‑inflammatory properties. The aim of this study was to investigate the effects of triptolide on lipopolysaccharide (LPS)‑induced acute lung injury (ALI) in mice and to explore the possible mechanisms. Mice were administered LPS intranasally to induce lung injury, and triptolide was administered intraperitoneally 1 h prior to the LPS challenge. Triptolide‑treated mice exhibited significantly reduced levels of leukocytes, myeloperoxidase activity and edema of the lung, as well as tumour necrosis factor‑α, interleukin (IL)‑1β and IL‑6 production in the bronchoalveolar lavage fluid compared with LPS‑treated mice. Additionally, western blot analysis showed that triptolide inhibited the LPS‑induced phosphorylation of nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor‑α and nuclear factor κ‑light‑chain‑enhancer of activated B cells‑p65 (NF‑κB p65) and the expression of Toll‑like receptor 4 (TLR4). In conclusion, the results from the present study suggest that the anti‑inflammatory effect of triptolide against LPS‑induced ALI may be due to its ability to inhibit the TLR4‑mediated NF‑κB signalling pathway. Triptolide may therefore be a promising potential therapeutic agent for ALI treatment, which may ultimately aid the clinical therapy for patients with ALI.

View Figures

View References

1	Chang CH, Kao CH, Chio CC, Lin CH, Lin MT and Chang CP: Attenuating heatstroke-induced acute lung inflammation, edema, and injury in rats by exercise preconditioning. J Trauma Acute Care Surg. 74:1052–1059. 2013. View Article : Google Scholar : PubMed/NCBI
2	Sharma S, Smith A, Kumar S, et al: Mechanisms of nitric oxide synthase uncoupling in endotoxin-induced acute lung injury: role of asymmetric dimethylarginine. Vascul Pharmacol. 52:182–190. 2010. View Article : Google Scholar : PubMed/NCBI
3	Fu PK, Yang CY, Tsai TH and Hsieh CL: Moutan cortex radicis improves lipopolysaccharide-induced acute lung injury in rats through anti-inflammation. Phytomedicine. 19:1206–1215. 2012. View Article : Google Scholar : PubMed/NCBI
4	Pati S, Gerber MH, Menge TD, et al: Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock. PLoS One. 6:e251712011. View Article : Google Scholar
5	Goodman RB, Pugin J, Lee JS and Matthay MA: Cytokine-mediated inflammation in acute lung injury. Cytokine Growth Factor Rev. 14:523–535. 2003. View Article : Google Scholar : PubMed/NCBI
6	Wen HL, Liang ZS, Zhang R and Yang K: Anti-inflammatory effects of triptolide improve left ventricular function in a rat model of diabetic cardiomyopathy. Cardiovasc Diabetol. 12:502013. View Article : Google Scholar : PubMed/NCBI
7	Seki H, Tasaka S, Fukunaga K, et al: Effect of Toll-like receptor 4 inhibitor on LPS-induced lung injury. Inflamm Res. 59:837–845. 2010. View Article : Google Scholar : PubMed/NCBI
8	Jeyaseelan S, Chu HW, Young SK, Freeman MW and Worthen GS: Distinct roles of pattern recognition receptors CD14 and Toll-like receptor 4 in acute lung injury. Infect Immun. 73:1754–1763. 2005. View Article : Google Scholar : PubMed/NCBI
9	Kennedy M, Phelps D and Ingenito E: Mechanisms of surfactant dysfunction in early acute lung injury. Exp Lung Res. 23:171–189. 1997. View Article : Google Scholar : PubMed/NCBI
10	Ben DF, Yu XY, Ji GY, et al: TLR4 mediates lung injury and inflammation in intestinal ischemia-reperfusion. J Surg Res. 174:326–333. 2012. View Article : Google Scholar : PubMed/NCBI
11	Huang D, Fang F and Xu F: Hyperoxia-induced up-regulation of Toll-like receptors expression in alveolar epithelial cells. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 23:645–649. 2011.(In Chinese).
12	Zhong WT, Wu YC, Xie XX, et al: Phillyrin attenuates LPS-induced pulmonary inflammation via suppression of MAPK and NF-κB activation in acute lung injury mice. Fitoterapia. 90:132–139. 2013.PubMed/NCBI
13	Matta R, Wang X, Ge H, Ray W, Nelin LD and Liu Y: Triptolide induces anti-inflammatory cellular responses. Am J Transl Res. 1:267–282. 2009.PubMed/NCBI
14	Qiu D and Kao PN: Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. f Drugs R D. 4:1–18. 2003. View Article : Google Scholar : PubMed/NCBI
15	Hoyle GW, Hoyle CI, Chen J, Chang W, Williams RW and Rando RJ: Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation. Am J Physiol Lung Cell Mol Physiol. 298:L830–L836. 2010. View Article : Google Scholar : PubMed/NCBI
16	Lee HF, Lee TS and Kou YR: Anti-inflammatory and neuroprotective effects of triptolide on traumatic brain injury in rats. Respir Physiol Neurobiol. 182:1–8. 2012. View Article : Google Scholar : PubMed/NCBI
17	Klawitter M, Quero L, Klasen J, et al: Triptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1β treated human intervertebral disc cells. Eur Spine J. 21(Suppl 6): S850–S859. 2012.PubMed/NCBI
18	Mei Z, Li X, Wu Q, Hu S and Yang X: The research on the anti-inflammatory activity and hepatotoxicity of triptolide-loaded solid lipid nanoparticle. Pharmacol Res. 51:345–351. 2005. View Article : Google Scholar : PubMed/NCBI
19	Jeyaseelan S, Chu HW, Young SK and Worthen GS: Transcriptional profiling of lipopolysaccharide-induced acute lung injury. Infect Immun. 72:7247–7256. 2004. View Article : Google Scholar : PubMed/NCBI
20	Guo Z, Li Q, Han Y, Liang Y, Xu Z and Ren T: Prevention of LPS-induced acute lung injury in mice by progranulin. Mediators Inflamm. 2012:5407942012.PubMed/NCBI
21	Fujino N, Kubo H, Suzuki T, et al: Administration of a specific inhibitor of neutrophil elastase attenuates pulmonary fibrosis after acute lung injury in mice. Exp Lung Res. 38:28–36. 2012. View Article : Google Scholar : PubMed/NCBI
22	Lewis CW, Taylor RG, Kubara PM, Marshall K, Meijer L and Golsteyn RM: A western blot assay to measure cyclin dependent kinase activity in cells or in vitro without the use of radioisotopes. FEBS Lett. 587:3089–3095. 2013. View Article : Google Scholar : PubMed/NCBI
23	Vallejo-Illarramendi A, Marciano DK and Reichardt LF: A novel method that improves sensitivity of protein detection in PAGE and Western blot. Electrophoresis. 34:1148–1150. 2013. View Article : Google Scholar : PubMed/NCBI
24	Lim YS, Chung MH, Park SH, et al: Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in rats: CT-pathologic correlation. Eur J Radiol. 62:227–234. 2007. View Article : Google Scholar : PubMed/NCBI
25	Parsons PE, Eisner MD, Thompson BT, et al; NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network. Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med. 33:1–6; discussion 230–232. 2005.
26	Trevejo JM, Marino MW, Philpott N, et al: TNF-alpha -dependent maturation of local dendritic cells is critical for activating the adaptive immune response to virus infection. Proc Natl Acad Sci USA. 98:12162–12167. 2001. View Article : Google Scholar : PubMed/NCBI
27	Ning J, Liu QF, Luo XD, Fan ZP and Zhang Y: Effect and mechanism of acute graft versus host disease on early diffuse murine lung injury following allogeneic stem cell transplantation. Sci China C Life Sci. 52:1016–1022. 2009. View Article : Google Scholar : PubMed/NCBI
28	Wu Y, Wan T, Zhou X, et al: Hsp70-like protein 1 fusion protein enhances induction of carcinoembryonic antigen-specific CD8⁺ CTL response by dendritic cell vaccine. Cancer Res. 65:4947–4954. 2005. View Article : Google Scholar : PubMed/NCBI
29	Zhang N, Wang Z, Tang X, et al: Type 1 T-cell responses in chlamydial lung infections are associated with local MIP-1alpha response. Cell Mol Immunol. 7:355–360. 2010. View Article : Google Scholar : PubMed/NCBI
30	Peng XM, Xie JH, Shuai B, et al: Inhalation of aerosolized perfluorocarbon combined with tetramethylpyrazine ameliorates hemodynamics and pulmonary histopathology in a porcine model of acute lung injury. Nan Fang Yi Ke Da Xue Xue Bao. 31:1382–1386. 2011.(In Chinese).