二氢丹参酮Ⅰ抑制脂磷壁酸(LTA)诱导的巨噬细胞炎症反应
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摘要
目的探究二氢丹参酮Ⅰ能否抑制脂磷壁酸(LTA)诱导的巨噬细胞炎症反应及其作用机制。方法以LTA为刺激剂,激活巨噬细胞,建立体外炎症模型,用Griees试剂法检测二氢丹参酮Ⅰ对LPS诱导的NO产生的影响,并用免疫蛋白印记法检测JNK、ERK、p-38、p65以及Akt磷酸化水平。结果二氢丹参酮Ⅰ能够抑制LTA诱导的NO产生,对JNK和ERK的活化无影响,但是可以抑制p38MAPK的活化,同时二氢丹参酮Ⅰ浓度依赖性地促进p65及Akt的活化。结论二氢丹参酮Ⅰ对LTA诱导的NO产生有显著抑制效果,其作用机制与抑制p38MAPK的活化有关。
Objective To determine whether Dihydrotanshinone □ can inhibit lipoteichoic acid(LTA) induced inflammation and explore the potential mechanism. Methods Macrophages were stimulated with LTA and NO production was measured by Griees reagent. In addition, the phospharylation of JNK, ERK, p-38, p65 and Akt were detected by Western blotting. Results Dihydrotanshinone □ inhibited LTA-induced NO production. Although Dihydrotanshinone □ didn't attenuate LTA-induced activation of JNK and ERK, Dihydrotanshinone □ decreased phospharylation of p38 MAPK. Moreover, Dihydrotanshinone □ dose-dependently promoted activation of p65 and Akt. Conclusion Dihydrotanshinone □ significantly inhibited LTA-induced NO production, which was associated with the reduction of phospharylation of p38 MAPK.
Objective To determine whether Dihydrotanshinone □ can inhibit lipoteichoic acid(LTA) induced inflammation and explore the potential mechanism. Methods Macrophages were stimulated with LTA and NO production was measured by Griees reagent. In addition, the phospharylation of JNK, ERK, p-38, p65 and Akt were detected by Western blotting. Results Dihydrotanshinone □ inhibited LTA-induced NO production. Although Dihydrotanshinone □ didn't attenuate LTA-induced activation of JNK and ERK, Dihydrotanshinone □ decreased phospharylation of p38 MAPK. Moreover, Dihydrotanshinone □ dose-dependently promoted activation of p65 and Akt. Conclusion Dihydrotanshinone □ significantly inhibited LTA-induced NO production, which was associated with the reduction of phospharylation of p38 MAPK.
引文
[1]王梦梦,吉兰芳,崔树娜.丹参功效的物质基础研究进展[J].中医学报,2019(05):944-949
[2] Xian Z, Razmovskinaumovski V, Chang D, et al. Synergistic Effects of Danshen(Salvia Miltiorrhiza Radix et Rhizoma)and Sanqi(Notoginseng Radix et Rhizoma)Combination in Inhibiting Inflammation Mediators in RAW264.7 Cells[J]. Biomed Research International, 2016, 2016(6):5758195.
[3] Akira, S., Uematsu, S., Takeuchi, O. Pathogen recognition and innate immunity[J]. Cell,2006(124):783-801.
[4] Liew, F.Y., Xu, D.M., Brint, E.K., O’Neill, L.A.J.. Negative regulation of toll-like receptor-mediated immune responses[J]. Nat. Rev. Immunol,2005,(5):446-458.
[5] Hacker H, Redecke V, Blagoev B, et al. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6[J]. Nature(London), 2005, 439(7073):204-207.
[6] Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival[J]. Journal of Cellular&Molecular Medicine, 2010, 9(1):59-71.
[7] Marta López-Peláez, Soria-Castro I, Lisardo Boscá, et al. Cot/tpl2 activity is required for TLR-induced activation of the Akt p70 S6k pathway in macrophages:Implications for NO synthase 2 expression[J]. European journal of immunology, 2011, 41(6):1733-1741.
[8] Wang X, Morris-Natschke S L, Lee K H. New developments in the chemistry and biology of the bioactive constituents of tanshen[J]. Medicinal Research Reviews, 2010, 27(1):133-148.
[9] Li M, Zhang L, Cai R L, et al. Lipid-soluble extracts from Salvia miltiorrhiza inhibit production of LPS-induced inflammatory mediators via NF-κB modulation in RAW 264.7 cells and perform antiinflammatory effects in vivo[J]. Phytotherapy Research Ptr, 2012, 26(8):1195-1204.
[10] Xian Z, Valentina R N, Dennis C, et al. Synergistic Effects of Danshen(Salvia Miltiorrhiza Radix et Rhizoma)and Sanqi(Notoginseng Radix et Rhizoma)Combination in Inhibiting Inflammation Mediators in RAW264.7Cells[J]. BioMed Research International, 2016, 2016:1-12.
[11] Jeon S J, Son K H, Kim Y S, et al. Inhibition of prostaglandin and nitric oxide production in lipopolysaccharide-treated RAW 264.7 cells by tanshinones from the roots ofSalvia miltiorrhizabunge[J]. Archives of Pharmacal Research, 2008, 31(6):758-763.
[12] Han Geun Kim), Seung Yeon Lee), Na Ra Kim), et al. Inhibitory Effects of Lactobacillus plantarum Lipoteichoic Acid(LTA)on Staphylococcus aureus LTA-Induced Tumor Necrosis Factor-Alpha Production[J]. Journal of Microbiology&Biotechnology, 2008, 18(6):1191.
[13] Deininger S, Stadelmaier A, Von Aulock S, et al. Definition of Structural Prerequisites for Lipoteichoic Acid-Inducible Cytokine Induction by Synthetic Derivatives[J]. The Journal of Immunology, 2003, 170(8):4134-4138.
[14] Ryu Y H, Baik J E, Yang J S, et al. Differential immunostimulatory effects of Gram-positive bacteria due to their lipoteichoic acids[J]. International Immunopharmacology, 2009, 9(1):0-133.
[15] Cot Marlène, Ray Aurélie, Martine G, et al. Lipoteichoic Acid in Streptomyces hygroscopicus:Structural Model and Immunomodulatory Activities[J]. PLoS ONE, 2011, 6(10):e26316-.
[2] Xian Z, Razmovskinaumovski V, Chang D, et al. Synergistic Effects of Danshen(Salvia Miltiorrhiza Radix et Rhizoma)and Sanqi(Notoginseng Radix et Rhizoma)Combination in Inhibiting Inflammation Mediators in RAW264.7 Cells[J]. Biomed Research International, 2016, 2016(6):5758195.
[3] Akira, S., Uematsu, S., Takeuchi, O. Pathogen recognition and innate immunity[J]. Cell,2006(124):783-801.
[4] Liew, F.Y., Xu, D.M., Brint, E.K., O’Neill, L.A.J.. Negative regulation of toll-like receptor-mediated immune responses[J]. Nat. Rev. Immunol,2005,(5):446-458.
[5] Hacker H, Redecke V, Blagoev B, et al. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6[J]. Nature(London), 2005, 439(7073):204-207.
[6] Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival[J]. Journal of Cellular&Molecular Medicine, 2010, 9(1):59-71.
[7] Marta López-Peláez, Soria-Castro I, Lisardo Boscá, et al. Cot/tpl2 activity is required for TLR-induced activation of the Akt p70 S6k pathway in macrophages:Implications for NO synthase 2 expression[J]. European journal of immunology, 2011, 41(6):1733-1741.
[8] Wang X, Morris-Natschke S L, Lee K H. New developments in the chemistry and biology of the bioactive constituents of tanshen[J]. Medicinal Research Reviews, 2010, 27(1):133-148.
[9] Li M, Zhang L, Cai R L, et al. Lipid-soluble extracts from Salvia miltiorrhiza inhibit production of LPS-induced inflammatory mediators via NF-κB modulation in RAW 264.7 cells and perform antiinflammatory effects in vivo[J]. Phytotherapy Research Ptr, 2012, 26(8):1195-1204.
[10] Xian Z, Valentina R N, Dennis C, et al. Synergistic Effects of Danshen(Salvia Miltiorrhiza Radix et Rhizoma)and Sanqi(Notoginseng Radix et Rhizoma)Combination in Inhibiting Inflammation Mediators in RAW264.7Cells[J]. BioMed Research International, 2016, 2016:1-12.
[11] Jeon S J, Son K H, Kim Y S, et al. Inhibition of prostaglandin and nitric oxide production in lipopolysaccharide-treated RAW 264.7 cells by tanshinones from the roots ofSalvia miltiorrhizabunge[J]. Archives of Pharmacal Research, 2008, 31(6):758-763.
[12] Han Geun Kim), Seung Yeon Lee), Na Ra Kim), et al. Inhibitory Effects of Lactobacillus plantarum Lipoteichoic Acid(LTA)on Staphylococcus aureus LTA-Induced Tumor Necrosis Factor-Alpha Production[J]. Journal of Microbiology&Biotechnology, 2008, 18(6):1191.
[13] Deininger S, Stadelmaier A, Von Aulock S, et al. Definition of Structural Prerequisites for Lipoteichoic Acid-Inducible Cytokine Induction by Synthetic Derivatives[J]. The Journal of Immunology, 2003, 170(8):4134-4138.
[14] Ryu Y H, Baik J E, Yang J S, et al. Differential immunostimulatory effects of Gram-positive bacteria due to their lipoteichoic acids[J]. International Immunopharmacology, 2009, 9(1):0-133.
[15] Cot Marlène, Ray Aurélie, Martine G, et al. Lipoteichoic Acid in Streptomyces hygroscopicus:Structural Model and Immunomodulatory Activities[J]. PLoS ONE, 2011, 6(10):e26316-.