Quercetin inhibits IL-1 beta-induced ICAM-1 expression in pulmonary epithelial cell line A549 through the MAPK pathways (original) (raw)

Abstract

Quercetin is a herbal flavonoid derived from various foods of plant origin and widely used as a major constituent of nutritional supplements. Quercetin has been shown to have anti-inflammatory properties and can play a role in anti-inflammatory procedure. Intercellular adhesion molecule-1 (ICAM-1) is one of the important pro-inflammatory factors, especially in early phage of inflammation. However, the mechanisms regulating ICAM-1 expression by quercetin in human A549 cells were still unclear. In this study, the inhibitory effect of quercetin on ICAM-1 expression by interleukin-1 beta (IL-1 beta)-stimulated A549 cells was investigated, and the roles of mitogen-activated protein kinases (MAPK) pathways were explored. Quercetin attenuated IL-1 beta-induced expression of ICAM-1 mRNA and protein in a dose-dependent manner. The experiment suggested that quercetin actively inhibited inhibitory protein of nuclear factor-kappa B (I kappa B) degradation, and nuclear factor-kappa B (NF-kappa B) activity. The c-fos and c-jun, components of activator protein-1 (AP-1), were mediated by MAPK pathways. ERK and p38 were involved in the c-fos mRNA expression, and JNK was involved in the c-jun mRNA expression. The inhibitory effect of quercetin on ICAM-1 expression was mediated by the sequential attenuation of the c-fos and c-jun mRNA expressions. These inhibitory effects were partially inhibited by SB203580, a specific inhibitor of p38 MAPK, but not by PD98059, a specific inhibitors of extracellular signal-regulated kinase (ERK), and SP600125, a specific inhibitor of c-Jun-N-terminal kinase (JNK). Taken together, these results suggest that quercetin negatively modulating ICAM-1 partly dependent on MAPK pathways.

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Abbreviations

ICAM-1:

Intercellular adhesion molecule-1

ERK:

Extracellular signal-regulated kinase

JNK:

c-jun NH2-terminal kinase

NF-kappa B:

Nuclear factor-kappa B

I kappa B:

Inhibitory protein of nuclear factor-kappa B

IL-1 beta:

Interleukin-1 beta

MAPK:

Mitogen activated protein kinase

AP-1:

Activator protein-1

TNF-alpha:

Tumor necrosis factor-alpha

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide

DMSO:

Dimethylsulfoxide

RT-PCR:

Reverse transcription-polymerase chain reaction

References

  1. Bravo L (1998) Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 56:317–333
    PubMed CAS Google Scholar
  2. Comalada M, Camuesco D, Sierra S, Ballester I, Xaus J, Galvez J, Zarzuelo A et al (2005) In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappa B pathway. Eur J Immunol 35:584–592
    Article PubMed CAS Google Scholar
  3. Hougee S, Sanders A, Faber J, Graus YM, van den Berg WB, Garssen J, Smit HF, Hoijer MA et al (2005) Decreased pro-inflammatory cytokine production by LPS-stimulated PBMC upon in vitro incubation with the flavonoids apigenin, luteolin or chrysin, due to selective elimination of monocytes/macrophages. Biochem Pharmacol 69:241–248
    Article PubMed CAS Google Scholar
  4. Staunton DE, Marlin SD, Stratowa C, Dustin ML, Springeret TA et al (1988) Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 5(2):925–933
    Article Google Scholar
  5. Kacimi R, Karliner JS, Koudssi F, Long CS et al (1998) Expression and regulation of adhesion molecules in cardiac cells by cytokines: response to acute hypoxia. Circ Res 82:576–586
    PubMed CAS Google Scholar
  6. Lee KS, Park SJ, Kim SR, Min KH, Jin SM, Lee HK et al (2006) Modulation of airway remodeling and airway inflammation by peroxisome proliferator-activated receptor gamma in a murine model of toluene diisocyanate-induced asthma. J Immunol 177:5248–5257
    PubMed CAS Google Scholar
  7. Stanciu LA, Djukanovic R (1998) The role of ICAM-1 on T-cells in the pathogenesis of asthma. Eur Respir J 11:949–957
    Article PubMed CAS Google Scholar
  8. Welty SE, Rivera JL, Elliston JF, Smith CV, Zeb T, Ballantyne CM, Montgomery CA, Hansen TN et al (1993) Increases in lung tissue expression of intercellular adhesion molecule-1 are associated with hyperoxic lung injury and inflammation in mice. Am J Respir Cell Mol Biol 9:393–400
    PubMed CAS Google Scholar
  9. Chiang CH et al (2006) Effects of anti-tumor necrosis factor-alpha and anti-intercellular adhesion molecule-1 antibodies on ischemia/reperfusion lung injury. Chin J Physiol 49:266–274
    PubMed CAS Google Scholar
  10. Nadadur SS, Schladweiler MC, Kodavanti UP et al (2000) A pulmonary rat gene array for screening altered expression profiles in air pollutant-induced lung injury. Inhal Toxicol 12:1239–1254
    Article PubMed CAS Google Scholar
  11. Yu HP, Shimizu T, Hsieh YC, Suzuki T, Choudhry MA, Schwacha MG, Chaudry IH et al (2006) Tissue-specific expression of estrogen receptors and their role in the regulation of neutrophil infiltration in various organs following trauma-hemorrhage. J Leukoc Biol 79:963–970
    Article PubMed CAS Google Scholar
  12. Wong C, Li ML, Wang CB, Ip WK, Tian YP, Lam CW et al (2006) House dust mite allergen Der p 1 elevates the release of inflammatory cytokines and expression of adhesion molecules in co-culture of human eosinophils and bronchial epithelial cells. Int Immunol 18:1327–1335
    Article PubMed CAS Google Scholar
  13. Kuldo JM, Westra J, Sgeirsdottir SA, Kok RJ, Oosterhuis K, Rots MG, Schouten JP, Limburg PC, Molema G et al (2005) Differential effects of NF-{kappa}B and p38 MAPK inhibitors and combinations thereof on TNF-{alpha}- and IL-1{beta}-induced proinflammatory status of endothelial cells in vitro. Am J Physiol Cell Physiol 289:C1229–C1239
    Article PubMed CAS Google Scholar
  14. Ishii H, Fujii T, Hogg JC, Hayashi S, Mukae H, Vincent R, van Eeden SF et al (2004) Contribution of IL-1 beta and TNF-alpha to the initiation of the peripheral lung response to atmospheric particulates (PM10). Am J Physiol Lung Cell Mol Physiol 287:L176–L183
    Article PubMed CAS Google Scholar
  15. Adiseshaiah P, Kalvakolanu DV, Reddy SP et al (2006) A JNK-independent signaling pathway regulates TNF alpha-stimulated, c-Jun-driven FRA-1 protooncogene transcription in pulmonary epithelial cells. J Immunol 177:7193–7202
    PubMed CAS Google Scholar
  16. Monje P, Hernandez-Losa J, Lyons RJ, Castellone MD, Gutkind JS et al (2005) Regulation of the transcriptional activity of c-Fos by ERK. A novel role for the prolyl isomerase PIN1. J Biol Chem 280:35081–35084
    Article PubMed CAS Google Scholar
  17. Tanos T, Marinissen MJ, Leskow FC, Hochbaum D, Martinetto H, Gutkind JS, Coso OA et al (2005) Phosphorylation of c-Fos by members of the p38 MAPK family. Role in the AP-1 response to UV light. J Biol Chem 280:18842–18852
    Article PubMed CAS Google Scholar
  18. Alcaraz MJ, Jimenez MJ, Valverde S, Sanz J, Rabanal RM, Villar A et al (1989) Anti-inflammatory compounds from Sideritis javalambrensis _n_-hexane extract. J Nat Prod 52:1088–1091
    Article PubMed CAS Google Scholar
  19. Garcia-Mediavilla V, Crespo I, Collado PS, Esteller A, Sanchez-Campos S, Tunon MJ, Gonzalez-Gallego J et al (2007) The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor-kappa B pathway in Chang Liver cells. Eur J Pharmacol 557:221–229
    Article PubMed CAS Google Scholar
  20. Gerritsen ME, Carley WW, Ranges GE, Shen CP, Phan SA, Ligon GF, Perry CA et al (1995) Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression. Am J Pathol 147:278–292
    PubMed CAS Google Scholar
  21. Rohn S, Rawel HM, Kroll J et al (2004) Antioxidant activity of protein-bound quercetin. J Agric Food Chem 52:4725–4729
    Article PubMed CAS Google Scholar
  22. Schmalhausen EV, Zhlobek EB, Shalova IN, Firuzi O, Saso L, Muronetz VI et al. (2007) Antioxidant and prooxidant effects of quercetin on glyceraldehyde-3-phosphate dehydrogenase. Food Chem Toxicol 45:1988–1993
    Article PubMed CAS Google Scholar
  23. Avila MA, Velasco JA, Cansado J, Notario V et al (1994) Quercetin mediates the down-regulation of mutant p53 in the human breast cancer cell line MDA-MB468. Cancer Res 54:2424–2428
    PubMed CAS Google Scholar
  24. Krol W, Dworniczak S, Pietsz G, Czuba ZP, Kunicka M, Kopacz M, Nowak D et al (2002) Synthesis and tumoricidal activity evaluation of new morin and quercetin sulfonic derivatives. Acta Pol Pharm 59:77–79
    PubMed CAS Google Scholar
  25. Orsolic N, Basic I (2005) Water-soluble derivative of propolis and its polyphenolic compounds enhance tumoricidal activity of macrophages. J Ethnopharmacol 102:37–45
    Article PubMed CAS Google Scholar
  26. Camacho SA, Heath WR, Carbone FR, Sarvetnick N, LeBon A, Karlsson L, Peterson PA, Webb SR et al (2001) A key role for ICAM-1 in generating effector cells mediating inflammatory responses. Nat Immunol 2:523–529
    Article PubMed CAS Google Scholar
  27. Tang MLK, Fiscus LC (2001) Important roles for l-selectin and ICAM-1 in the development of allergic airway inflammation in asthma. Pulm Pharmacol Ther 14:203–210
    Article PubMed CAS Google Scholar

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Acknowledgments

This study was supported by Grants #30425007, 30370627, 30670921 from National Natural Science Foundation of China and 00–722, 06–834 from China Medical Board of New York to Dr. F.Q. Wen.

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Authors and Affiliations

  1. Department of Lab Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China
    Binwu Ying, Xingbo Song, Hong Fan & Xiaojun Lu
  2. Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China
    Ting Yang, Xiaobo Hu, Lijuan Chen, Deyun Cheng, Tao Wang, Daishun Liu, Dan Xu, Yuquan Wei & Fuqiang Wen

Authors

  1. Binwu Ying
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  2. Ting Yang
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  3. Xingbo Song
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  4. Xiaobo Hu
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  5. Hong Fan
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  6. Xiaojun Lu
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  7. Lijuan Chen
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  8. Deyun Cheng
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  9. Tao Wang
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  10. Daishun Liu
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  11. Dan Xu
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  12. Yuquan Wei
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  13. Fuqiang Wen
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Correspondence toFuqiang Wen.

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Binwu Ying and Ting Yang have contributed equally to this work.

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Ying, B., Yang, T., Song, X. et al. Quercetin inhibits IL-1 beta-induced ICAM-1 expression in pulmonary epithelial cell line A549 through the MAPK pathways.Mol Biol Rep 36, 1825–1832 (2009). https://doi.org/10.1007/s11033-008-9386-1

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