BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Sulforaphane inhibits the Th2 immune response in ovalbumin-induced asthma

  • Park, Jun-Ho (Department of Thoracic and Cardiovascular Surgery, Busan Medical Center) ;
  • Kim, Jong-Won (Department of Thoracic and Cardiovascular Surgery, Busan Medical Center) ;
  • Lee, Chang-Min (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Kim, Yeong-Dae (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Pusan National University) ;
  • Chung, Sung-Woon (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Pusan National University) ;
  • Jung, In-Duk (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Noh, Kyung-Tae (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Park, Jin-Wook (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Heo, Deok-Rim (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Shin, Yong-Kyoo (Department of Pharmacology, Chungang University College of Medicine) ;
  • Seo, Jong-Keun (Department of Dermatology, Busan Paik Hospital, College of Medicine, Inje University) ;
  • Park, Yeong-Min (Department of Microbiology and Immunology, Pusan National University School of Medicine)
  • Received : 2012.01.19
  • Accepted : 2012.02.06
  • Published : 2012.05.31
Download PDF
⟨ Previous Next ⟩

Abstract

Sulforaphane (1-isothiocyanato-4-(methylsulfinyl)-butane), belonging to a family of natural compounds that are abundant in broccoli, has received significant therapeutic interest in recent years. However, the molecular basis of its effects remains to be elucidated. In this study, we attempt to determine whether sulforaphane regulates the inflammatory response in an ovalbumin (OVA)-induced murine asthma model. Mice were sensitized with OVA, treated with sulforaphane, and then challenged with OVA. Sulforaphane administration significantly alleviated the OVA-induced airway hyperresponsiveness to inhaled methacholine. Additionally, sulforaphane suppressed the increase in the levels of SOCS-3 and GATA-3 and IL-4 expression in the OVA-challenged mice. Collectively, our results demonstrate that sulforaphane regulates Th2 immune responses. This sutdy provides novel insights into the regulatory role of sulforaphane in allergen-induced Th2 inflammation and airway responses, which indicates its therapeutic potential for asthma and other allergic diseases.

Keywords

References

  1. Corrigan, C. J. and Kay. A. B. (1992) T cells and eosinophils in the pathogenesis of asthma. Immunol. Today 13, 501-507. https://doi.org/10.1016/0167-5699(92)90026-4
  2. Karp, M. and Oker-Blom, C. (1999) A streptavidin-luciferase fusion protein: comparisons and applications. Biomol. Eng. 16, 101-104. https://doi.org/10.1016/S1050-3862(99)00039-X
  3. Punnonen, J., Aversa, G., Cocks, B. G. and de Vries, J. E. (1994) Role of interleukin-4 and interleukin-13 in synthesis of IgE and expression of CD23 by human B cells. Allergy 49, 576-586 https://doi.org/10.1111/j.1398-9995.1994.tb00122.x
  4. Renz, H., Bradley, K., Saloga, J., Loader, J., Larsen, G. L. and Gelfand, E. W. (1993) T cells expressing specific V beta elements regulate immunoglobulin E production and airways responsiveness in vivo. J. Exp. Med. 177, 1175-1180. https://doi.org/10.1084/jem.177.4.1175
  5. Iwamoto, I., Nakajima, H., Endo, H. and Yoshida, S. (1993) Interferon gamma regulates antigen-induced eosinophil recruitment into the mouse airways by inhibiting the infiltration of CD4+ T cells. J. Exp. Med. 177, 573-576. https://doi.org/10.1084/jem.177.2.573
  6. Saito, H., Hatake, K., Dvorak, A. M., Leiferman, K. M., Donnenberg, A. D., Arai, N., Ishizaka, K. and Ishizaka, T. (1988) Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins. Proc. Natl. Acad. Sci. U.S.A. 85, 2288-2292. https://doi.org/10.1073/pnas.85.7.2288
  7. Sur, S., Lam, J., Bouchard, P., Sigounas, A., Holbert, D. and Metzger, W. J. (1996) Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses. J. Immunol. 157, 4173-4180.
  8. Tanaka, H., Komai, M., Nagao, K., Ishizaki, M., Kajiwara, D., Takatsu, K., Delespesse, G. and Nagai, H. (2004) Role of interleukin-5 and eosinophils in allergen-induced airway remodeling in mice. Am. J. Respir. Cell. Mol. Biol. 31, 62-68. https://doi.org/10.1165/rcmb.2003-0305OC
  9. Bousquet, J., Chanez, P., Lacoste, J. Y., Barneon, G., Ghavanian, N., Enander, I., Venge, P., Ahlstedt, S., Simony-Lafontaine, J. and Godard, P. (1990) Eosinophilic inflammation in asthma. N. Engl. J. Med. 323, 1033-1039. https://doi.org/10.1056/NEJM199010113231505
  10. Mapp, C. E. (1989) Assessment of occupational asthma. Med. Lav. 80, 275-280.
  11. Mapp, C. E., Boschetto, P., Dal Vecchio, L., Maestrelli, P. and Fabbri, L. M. (1988) Occupational asthma due to isocyanates. Eur. Respir. J. 1, 273-279.
  12. Busse, W. W., Calhoun, W. F. and Sedgwick, J. D. (1993) Mechanism of airway inflammation in asthma. Am. Rev. Respir. Dis. 147, S20-S24. https://doi.org/10.1164/ajrccm/147.6_Pt_2.S20
  13. Kay, A. B. (1991) Asthma and inflammation. J. Allergy Clin. Immunol. 87, 893-910. https://doi.org/10.1016/0091-6749(91)90408-G
  14. Murphy, G. and Docherty, A. J. (1992) The matrix metalloproteinases and their inhibitors. Am. J. Respir. Cell. Mol. Biol. 7, 120-125. https://doi.org/10.1165/ajrcmb/7.2.120
  15. Okada, S., Kita, H., George, T. J., Gleich, G. J. and Leiferman, K. M. (1997) Migration of eosinophils through basement membrane components in vitro: role of matrix metalloproteinase- 9. Am. J. Respir. Cell. Mol. Biol. 17, 519-528. https://doi.org/10.1165/ajrcmb.17.4.2877
  16. Roberts, A. W., Robb, L., Rakar, S., Hartley, L., Cluse, L., Nicola, N. A., Metcalf, D., Hilton, D. J. and Alexander, W. S. (2001) Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3. Proc. Natl. Acad. Sci. U.S.A. 98, 9324-9329. https://doi.org/10.1073/pnas.161271798
  17. Seki, Y., Inoue, H., Nagata, N., Hayashi, K., Fukuyama, S., Matsumoto, K., Komine, O., Hamano, S., Himeno, K., Inagaki-Ohara, K., Cacalano, N., O'Garra, A., Oshida, T., Saito, H., Johnston, J. A., Yoshimura, A. and Kubo, M. (2003) SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat. Med. 9, 1047-1054. https://doi.org/10.1038/nm896
  18. Mi, L., Wang, X., Govind, S., Hood, B. L., Veenstra, T. D., Conrads, T. P., Saha, D. T., Goldman, R. and Chung, F. L. (2007) The role of protein binding in induction of apoptosis by phenethyl isothiocyanate and sulforaphane in human non-small lung cancer cells. Cancer Res. 67, 6409-6416. https://doi.org/10.1158/0008-5472.CAN-07-0340
  19. Moon, D. O., Kim, M. O., Kang, S. H., Choi, Y. H. and Kim, G. Y. (2009) Sulforaphane suppresses TNF-alpha- mediated activation of NF-kappaB and induces apoptosis through activation of reactive oxygen species-dependent caspase-3. Cancer Lett. 274, 132-142. https://doi.org/10.1016/j.canlet.2008.09.013
  20. Riedl, M. A., Saxon, A. and Diaz-Sanchezm D. (2009) Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. Clin. Immunol. 130, 244-251. https://doi.org/10.1016/j.clim.2008.10.007
  21. Yoon, M. S., Lee, J. S., Choi, B. M., Jeong, Y. I., Lee, C. M., Park, J. H., Moon, Y., Sung, S. C., Lee, S. K., Chang, Y. H., Chung, H. Y. and Park, Y. M. (2006) Apigenin inhibits immunostimulatory function of dendritic cells: Implication of immunotherapeutic adjuvant. Mol. Pharmacol. 70, 1033-1044. https://doi.org/10.1124/mol.106.024547
  22. Kim, G. Y., Cho, H., Ahn, S. C., Oh, Y. H., Lee, C. M. and Park, Y. M. (2004) Resveratrol inhibits phenotypic and functional maturation of murine bone marrow-derived dendritic cells. Int. Immunopharmacol. 4, 245-253. https://doi.org/10.1016/j.intimp.2003.12.009
  23. Chen, C. C., Chow, M. P., Huang, W. C., Lin, Y. C. and Chang, Y. J. (2004) Flavonoids inhibit tumor necrosis factor- alpha-induced up-regulation of intercellular adhesion molecule-1 (ICAM-1) in respiratory epithelial cells through activator protein-1 and nuclear factor-kappaB: structure- activity relationships. Mol. Pharmacol. 66, 683-693.
  24. Grzelewska-Rzymowska, I., Grzegorczyk, J., Grabski, W., Kroczynska-Bednarek, J., Kuzminska, B. and Rozniecki, J. (1996) Chemotactic serum activity for neutrophils and eosinophils and spontaneous production of histamine releasing factor in patients with seasonal bronchial asthma treated with nedocromil sodium. Pneumonol. Alergol. Pol. 64, 132-140.
  25. Lee, C. M., Chang, J. H., Moon, D. O., Choi, Y. H., Choi, I. W., Park, Y. M. and Kim, G. Y. (2008) Lycopene suppresses ovalbumin-induced airway inflammation in a murine model of asthma. Biochem. Biophys. Res. Commun. 374, 248-252. https://doi.org/10.1016/j.bbrc.2008.07.032

Cited by

  1. A Randomized Controlled Trial of the Effect of Broccoli Sprouts on Antioxidant Gene Expression and Airway Inflammation in Asthmatics vol.4, pp.5, 2016, https://doi.org/10.1016/j.jaip.2016.03.012
  2. The potential role of some phytochemicals in recognition of mitochondrial damage-associated molecular patterns vol.30, 2016, https://doi.org/10.1016/j.mito.2016.06.001
  3. The effect of safranal, a constituent of Crocus sativus (saffron), on tracheal responsiveness, serum levels of cytokines, total NO and nitrite in sensitized guinea pigs vol.66, pp.1, 2014, https://doi.org/10.1016/j.pharep.2013.08.004
  4. Inflammation and airway hyperresponsiveness after chlorine exposure are prolonged by Nrf2 deficiency in mice vol.102, 2017, https://doi.org/10.1016/j.freeradbiomed.2016.11.017
  5. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates airway epithelial barrier integrity vol.64, 2015, https://doi.org/10.1016/j.alit.2015.06.004
  6. Immunomodulatory Activities of a Concentrated Fruit and Vegetable Juice Tested in a Randomized, Placebo-Controlled, Double-Blind Clinical Trial in Healthy Volunteers vol.05, pp.04, 2014, https://doi.org/10.4236/fns.2014.54041
  7. Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways vol.16, pp.1, 2015, https://doi.org/10.1186/s12931-015-0253-z
  8. Perspectives on epigenetic-based immune intervention for rheumatic diseases vol.15, pp.2, 2013, https://doi.org/10.1186/ar4167
  9. Epigenetic-based immune intervention for rheumatic diseases vol.6, pp.2, 2014, https://doi.org/10.2217/epi.13.87
  10. A Novel Compound ITC-3 Activates the Nrf2 Signaling and Provides Neuroprotection in Parkinson’s Disease Models vol.28, pp.4, 2015, https://doi.org/10.1007/s12640-015-9550-z
  11. Paracellular Transport of Sulforaphane across Caco-2 Cell Monolayers vol.22, pp.1, 2016, https://doi.org/10.3136/fstr.22.127
  12. Health Functionality of Organosulfides: A Review vol.19, pp.3, 2016, https://doi.org/10.1080/10942912.2015.1034281
  13. Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response vol.265, pp.3, 2012, https://doi.org/10.1016/j.taap.2012.08.028
  14. Cruciferous Vegetables Have Variable Effects on Biomarkers of Systemic Inflammation in a Randomized Controlled Trial in Healthy Young Adults vol.144, pp.11, 2014, https://doi.org/10.3945/jn.114.197434
  15. Acrolein and thiol-reactive electrophiles suppress allergen-induced innate airway epithelial responses by inhibition of DUOX1 and EGFR vol.311, pp.5, 2016, https://doi.org/10.1152/ajplung.00276.2016
  16. Effects of a Standard American Diet and an anti-inflammatory diet in male and female mice vol.22, pp.7, 2018, https://doi.org/10.1002/ejp.1207
  17. Role of Nrf2 and Its Activators in Respiratory Diseases vol.2019, pp.1942-0994, 2019, https://doi.org/10.1155/2019/7090534