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Effects of All-Trans Retinoic Acid on Th1- and Th2-Related Chemokines Production in Monocytes

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Abstract

Low vitamin C and reduced alpha-carotene intake are associated with increased asthma risk in children. In addition, mean serum vitamin A concentrations are significantly lower in asthmatic children than in controls. All-trans retinoic acid (ATRA) is a derivative of vitamin A. Macrophage-derived chemokine (MDC) is a T helper cell-type 2 (Th2)-related chemokine involved in the recruitment of Th2 cells toward inflammatory sites. On the other hand, Th1-related chemokine, interferon-inducible protein 10 (IP-10)/CXCL10 is also important in allergic inflammation. Both Th1- and Th2-related chemokines play an important role in allergic asthma. To survey whether ATRA and ascorbic acid effect Th1- and Th2-related chemokine expression in monocytes. To test this, THP-1 cells were pre-treated with ATRA or ascorbic acid and stimulated by lipopolysaccharide (LPS) or poly I:C. Supernatants were measured for Th2-related (MDC) and Th1-related (IP-10) chemokine concentrations by ELISA. The effects of ATRA on mitogen-activated protein kinase (MAPK) and NFkb were evaluated with Western blotting. After stimulation, ATRA significantly down-regulated MDC and IP-10 in a dose-dependent manner. Similarly, ascorbic acid reduced the LPS-induced changes in MDC but only with a high dose. However, asorbic acid had no effect on IP-10 changes either induced by LPS or poly I:C. RT-PCR showed ATRA inhibited IP-10 expression through decreasing the level of transcription. Furthermore, ATRA suppressed the expression of LPS-stimulated c-Raf, MKK1/2 and ERK expression of THP-1 cells. In conclusion, ATRA suppressed Th2- and Th1-related chemokines expression in THP-1 cells, at least in part via the c-Raf-MKK1/2-ERK/MAPK pathway.

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References

  1. Barnes, P. J., K. F. Chung, and C. P. Page. 1998. Inflammatory mediators of asthma: an update. Pharmacol. Rev. 50:515–596.

    PubMed  CAS  Google Scholar 

  2. Crimi, E., D. Gaffi, E. Frittoli, B. Borgonovo, and S. E. Burastero. 1997. Depletion of circulating allergen specific TH2 T lymphocytes after allergen exposure in asthma. J. Allergy Clin. Immunol. 99:788–797. doi:10.1016/S0091-6749(97)80013-9.

    Article  PubMed  CAS  Google Scholar 

  3. Harik-Khan, R. I., D. C. Muller, and R. A. Wise. 2004. Serum vitamin levels and the risk of asthma in children. Am. J. Epidemiol. 159:351–357. doi:10.1093/aje/kwh053.

    Article  PubMed  Google Scholar 

  4. Mizuno, Y., T. Furusho, A. Yoshida, H. Nakamura, T. Matsuura, and Y. Eto. 2006. Serum vitamin A concentrations in asthmatic children in Japan. Pediatr. Int. 48:261–264. doi:10.1111/j.1442-200X.2006.02200.x.

    Article  PubMed  CAS  Google Scholar 

  5. Takamura, K., Y. Nasuhara, M. Kobayashi, T. Betsuyaku, Y. Tanino, I. Kinoshita, E. Yamaguchi, S. Matsukura, R. P. Schleimer, and M. Nishimura. 2004. Retinoic acid inhibits interleukin-4-induced eotaxin production in a human bronchial epithelial cell line. Am. J. Physiol. Lung Cell Mol. Physiol. 286:L777–L785. doi:10.1152/ajplung.00289.2003.

    Article  PubMed  CAS  Google Scholar 

  6. Pilette, C., J. N. Francis, S. J. Till, and S. R. Durham. 2004. CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge. Eur. Respir. J. 23:876–884. doi:10.1183/09031936.04.00102504.

    Article  PubMed  CAS  Google Scholar 

  7. Liu, L., N. N. Jarjour, W. W. Buss, and E. A. Kelly. 2004. Enhanced generation of helper T type 1 and 2 chemokines in allergen-induced asthma. Am. J. Respir. Crit. Care Med. 169:1118–1124. doi:10.1164/rccm.200312-1659OC.

    Article  PubMed  Google Scholar 

  8. Hung, C. H., C. Y. Li, Y. S. Lai, P. C. Hsu, Y. M. Hua, and K. D. Yang. 2005. Discrepant clinical responses and blood chemokine profiles between two non-steroidal anti-inflammatory medications for children with mild persistent asthma. Pediatr. Allergy Immunol. 16:306–309.

    PubMed  Google Scholar 

  9. Lai, S. T., C. H. Hung, Y. M. Hua, S. H. Hsu, Y. J. Jong, and J. L. Suen. 2008. T-helper 1-related chemokines in the exacerbation of childhood asthma. Pediatr. Int. 50:99–102. doi:10.1111/j.1442-200X.2007.02533.x.

    Article  PubMed  CAS  Google Scholar 

  10. Hung, C. H., J. L. Suen, Y. M. Hua, W. Chiang, H. C. Chang, C. N. Chen, and Y. J. Jong. 2007. Suppressive effects of ketotifen on Th1- and Th2-related chemokines of monocytes. Pediatr. Allergy Immunol. 18:378–384. doi:10.1111/j.1399-3038.2007.00535.x.

    Article  PubMed  Google Scholar 

  11. Tudhope, S. J., T. K. Finney-Hayward, A. G. Nicholson, R. J. Mayer, M. S. Barnette, P. J. Barnes, and L. E. Donnelly. 2008. Different mitogen-activated protein kinase-dependent cytokine responses in cells of the monocyte lineage. J. Pharmacol. Exp. Ther. 324:306–312. doi:10.1124/jpet.107.127670.

    Article  PubMed  CAS  Google Scholar 

  12. Jones, N. C., Y. V. Fedorov, R. S. Rosenthal, and B. B. Olwin. 2001. ERK1/2 is required for myoblast proliferation but is dispensable for muscle gene expression and cell fusion. J. Cell Physiol. 186:104–115. doi:10.1002/1097-4652(200101)186:1<104::AID-JCP1015>3.0.CO;2-0.

    Article  PubMed  CAS  Google Scholar 

  13. Seiss, S. T. 2002. Eat dirt-the hygiene hypothesis and allergic diseases. N. Engl. J. Med. 347:930–931. doi:10.1056/NEJMe020092.

    Article  Google Scholar 

  14. Marks, G. B., S. Mihrshahi, A. S. Kemp, E. R. Tovey, K. Webb, C. Almqvist, R. D. Ampon, D. Crisafulli, E. G. Belousova, C. M. Mellis, J. K. Peat, and S. R. Leeder. 2006. Prevention of asthma during the first 5 years of life: a randomized controlled trial. J. Allergy Clin. Immunol. 118:53–61. doi:10.1016/j.jaci.2006.04.004.

    Article  PubMed  CAS  Google Scholar 

  15. Dawson, H. D., G. Collins, R. Pyle, M. Key, A. Weeraratna, V. Deep-Dixit, C. N. Nadal, and D. D. Taub. 2006. Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes. BMC Immunol. 7:27. doi:10.1186/1471-2172-7-27.

    Article  PubMed  Google Scholar 

  16. Kull, I., A. Bergström, E. Melén, G. Lilja, M. van Hage, G. Pershagen, and M. Wickman. 2006. Early-life supplementation of vitamins A and D, in water-soluble form or in peanut oil, and allergic diseases during childhood. J. Allergy Clin. Immunol. 118:1299–1304. doi:10.1016/j.jaci.2006.08.022.

    Article  PubMed  CAS  Google Scholar 

  17. McGowan, S. E. 2007. Vitamin A deficiency increases airway resistance following C-fiber stimulation. Respir. Physiol. Neurobiol. 157:281–289. doi:10.1016/j.resp.2007.01.011.

    Article  PubMed  CAS  Google Scholar 

  18. Ko, J., C. Y. Yun, J. S. Lee, D. H. Kim, J. E. Yuk, and I. S. Kim. 2006. Differential regulation of CC chemokine receptors by 9-cis retinoic acid in the human mast cell line, HMC-1. Life Sci. 79:1293–1300. doi:10.1016/j.lfs.2006.03.046.

    Article  PubMed  CAS  Google Scholar 

  19. Reed, C. E., and D. K. Milton. 2001. Endotoxin-stimulated innate immunity: a contributing factor for asthma. J. Allergy Clin. Immunol. 108:157–166. doi:10.1067/mai.2001.116862.

    Article  PubMed  CAS  Google Scholar 

  20. Bochner, B. S., S. A. Hudson, H. Q. Xiao, and M. C. Liu. 2003. Release of both CCR4-active and CXCR3-active chemokines during human allergic pulmonary late-phase reactions. J. Allergy Clin. Immunol. 112:930–934. doi:10.1016/j.jaci.2003.08.012.

    Article  PubMed  CAS  Google Scholar 

  21. Hung, C. H., C. Y. Li, Y. M. Hua, K. D. Yang, and Y. J. Jong. 2006. Effects of leukotriene receptor antagonists on monocyte chemotaxis, p38 and cytoplasmic calcium. Pediatr Allergy Immunol. 17:250–258. doi:10.1111/j.1399-3038.2006.00385.x.

    Article  PubMed  Google Scholar 

  22. Wark, P. A., F. Bucchieri, S. L. Johnston, P. G. Gibson, L. Hamilton, J. Mimica, G. Zummo, S. T. Holgate, J. Attia, A. Thakkinstian, and D. E. Davies. 2007. IFN-gamma-induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations. J. Allergy Clin. Immunol. 120:586–593. doi:10.1016/j.jaci.2007.04.046.

    Article  PubMed  CAS  Google Scholar 

  23. Sugiyama, T., K. Hoshino, M. Saito, T. Yano, I. Sasaki, C. Yamazaki, S. Akira, and T. Kaisho. 2008. Immunoadjuvant effects of polyadenylic:polyuridylic acids through TLR3 and TLR7. Int. Immunol. 20:1–9. doi:10.1093/intimm/dxm112.

    Article  PubMed  CAS  Google Scholar 

  24. Yanai, M., K. Sato, N. Aoki, Y. Takiyama, K. Oikawa, H. Kobayashi, S. Kimura, Y. Harabuchi, and M. Tateno. 2007. The role of CCL22/macrophage-derived chemokine in allergic rhinitis. Clin Immunol. 125:291–298. doi:10.1016/j.clim.2007.08.002.

    Article  PubMed  CAS  Google Scholar 

  25. Leung, T. F., G. W. Wong, F. W. Ko, C. W. Lam, and T. F. Fok. 2004. Increased macrophage-derived chemokine in exhaled breath condensate and plasma from children with asthma. Clin. Exp. Allergy. 34:786–791. doi:10.1111/j.1365-2222.2004.1951.x.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Chih-Hsing Hung.

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Supported by a grant from the Chi-Mei Medical Center and Kaohsiung Medical University Research Foundation (CM-KMU_ X096009)

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Tsai, YC., Chang, HW., Chang, TT. et al. Effects of All-Trans Retinoic Acid on Th1- and Th2-Related Chemokines Production in Monocytes. Inflammation 31, 428–433 (2008). https://doi.org/10.1007/s10753-008-9095-x

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