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  • Original Paper
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Suppression of UVB-induced phosphorylation of mitogen-activated protein kinases and nuclear factor kappa B by green tea polyphenol in SKH-1 hairless mice

Oncogene volume 22, pages 9254–9264 (2003)Cite this article

Abstract

Studies from our laboratory have shown that epigallocatechin-3-gallate, the major polyphenol present in green tea, inhibits ultraviolet (UV)B-exposure-mediated phosphorylation of mitogen-activated protein kinases (MAPKs) (Toxicol. Appl. Pharmacol. 176: 110–117, 2001) and activation of nuclear factor kappa B (NF-κB) (Oncogene 22: 1035–1044, 2003) pathways in normal human epidermal keratinocytes. This study was designed to investigate the relevance of these findings to the in vivo situations in SKH-1 hairless mouse model, which is regarded to have relevance to human situations. SKH-1 hairless mice were topically treated with GTP (5 mg/0.2 ml acetone/mouse) and were exposed to UVB 30 min later (180 mJ/cm2). These treatments were repeated every alternate day for 2 weeks, for a total of seven treatments. The animals were killed 24 h after the last UVB exposure. Topical application of GTP resulted in significant decrease in UVB-induced bifold-skin thickness, skin edema and infiltration of leukocytes. Employing Western blot analysis and immunohistochemical studies, we found that GTP resulted in inhibition of UVB-induced: (i) phosphorylation of extracellular-signal-regulated kinases (ERK1/2), (ii) c-Jun N-terminal kinases, and (iii) p38 protein expression. Since NF-κB plays a major role in inflammation and cell proliferation, we assessed the effect of GTP on UVB-mediated modulations in the NF-κB pathway. Our data demonstrated that GTP inhibited UVB-induced: (i) activation of NF-κB, (ii) activation of IKKα, and (iii) phosphorylation and degradation of IκBα. Our data suggest that GTP protects against the adverse effects of UV radiation via modulations in MAPK and NF-κB signaling pathways, and provides molecular basis for the photochemopreventive effect of GTP in an in vivo animal model system.

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References

  • Adderley SR and Fitzgerald DJ . (1999). J. Biol. Chem., 274, 5038–5046.

  • Afaq F, Adhami VM, Ahmad N and Mukhtar H . (2002). Front. Biosci., 7, d784–d792.

  • Afaq F, Adhami VM, Ahmad N and Mukhtar H . (2003a). Oncogene, 22, 1035–1044.

  • Afaq F, Adhami VM and Ahmad N . (2003b). Toxicol. Appl. Pharmacol., 186, 28–37.

  • Afaq F and Mukhtar H . (2002). Skin Pharmacol. Appl. Skin Physiol., 15, 297–306.

  • Agarwal R, Katiyar SK, Zaidi SI and Mukhtar H . (1992). Cancer Res., 52, 3582–3588.

  • Ahmad N, Gupta S and Mukhtar H . (2000). Arch. Biochem. Biophys., 376, 338–346.

  • Ananthaswamy HN, Loughlin SM, Cox P, Evans RL, Ullrich SE and Kripke ML . (1997). Nat. Med., 3, 510–514.

  • Bachelor MA, Silvers AL and Bowden GT . (2002). Oncogene, 21, 7092–7099.

  • Baeuerle PA and Baltimore D . (1988). Science, 242, 540–546.

  • Baeuerle PA and Baltimore D . (1996). Cell, 87, 13–20.

  • Balasubramanian S, Kim KH, Ahmad N and Mukhtar H . (1999). Oncogene, 18, 1297–1302.

  • Baldwin AS . (1996). Annu. Rev. Immunol., 14, 649–683.

  • Bost F, McKay R, Dean N and Mercola D . (1997). J. Biol. Chem., 272, 33422–33429.

  • Carter AB, Knudtson KL, Monick MM and Hunninghake GW . (1999). J. Biol. Chem., 274, 30858–30863.

  • Cavigelli M, Dolfi F, Claret FX and Karin M . (1995). EMBO J., 14, 5957–5964.

  • Chang L and Karin M . (2001). Nature, 410, 37–40.

  • Chen N, Ma W, Huang C and Dong Z . (1999). J. Biol. Chem., 274, 15389–15394.

  • Chen W, Borchers AH, Dong Z, Powell MB and Bowden GT . (1998). J. Biol. Chem., 273, 32176–32181.

  • Chen W, Tang Q, Gonzales MS and Bowden GT . (2001). Oncogene, 20, 3921–3926.

  • Chen YC, Shen SC, Lee WR, Lin HY, Ko CH and Lee TJ . (2002). J. Cell. Biochem., 86, 331–339.

  • Chouinard N, Valerie K, Rouabhia M and Huot J . (2002). Biochem. J., 365, 133–145.

  • Clydesdale GJ, Dandie GW and Muller HK . (2001). Immunol. Cell Biol., 79, 547–568.

  • de Gruijl FR . (2002). Skin Pharmacol. Appl. Skin Physiol., 15, 316–320.

  • Derijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M and Davis RJ . (1994). Cell, 76, 1025–1037.

  • Dhar A, Young MR and Colburn NH . (2002). Mol. Cell. Biochem., 234-235, 185–193.

  • Dubois B, Lamy PJ, Chemin K, Lachaux A and Kaiserlian D . (2001). Cell. Immunol., 214, 173–183.

  • Elmets CA, Singh D, Tubesing K, Matsui M, Katiyar SK and Mukhtar H . (2001). J. Am. Acad. Dermatol., 44, 425–432.

  • F’guyer S, Afaq F and Mukhtar H . (2003). Photoderm. Photoimmunol. Photomed., 19, 56–72.

  • Garg A and Aggarwal BB . (2002). Leukemia, 16, 1053–1068.

  • Gensler HL and Welch K . (1992). Carcinogenesis, 1, 9–13.

  • Greenlee RT, Murray T, Bolden S and Wigo PA . (2000). CA Cancer J. Clin., 50, 7–33.

  • Hildesheim J, Bulavin DV, Anver MR, Alvord WG, Hollander MC, Vardanian L and Fornace Jr AJ . (2002). Cancer Res., 62, 7305–7315.

  • Huang C, Ma W, Bowden GT and Dong Z . (1996). J. Biol. Chem., 271, 31262–31268.

  • Huang C, Ma WY, Young MR, Colburn N and Dong Z . (1998). Proc. Natl. Acad. Sci. USA, 95, 156–161.

  • Iordanov M, Bender K, Ade T, Schmid W, Sachsenmaier C, Engel K, Gaestel M, Rahmsdorf HJ and Herrlich P . (1997). EMBO J., 16, 1009–1022.

  • Iordanov MS, Choi RJ, Ryabinina OP, Dinh TH, Bright RK and Magun BE . (2002). Mol. Cell. Biol., 22, 5380–5394.

  • Jemal A, Devesa SS, Fears TR and Hartge P . (2000). J. Natl. Cancer Inst., 92, 811–818.

  • Kang S, Chung JH, Lee JH, Fisher GJ, Wan YS, Duell EA and Voorhees JJ . (2003). J. Invest. Dermatol., 120, 835–841.

  • Karin M . (1995). J. Biol. Chem., 270, 16483–16486.

  • Katiyar SK, Afaq F, Azizuddin K and Mukhtar H . (2001a). Toxicol. Appl. Pharmacol., 176, 110–117.

  • Katiyar SK, Afaq F, Perez A and Mukhtar H . (2001b). Carcinogenesis, 22, 287–294.

  • Katiyar SK, Agarwal R, Wood GS and Mukhtar H . (1992). Cancer Res., 52, 6890–6897.

  • Katiyar SK, Elmets CA, Agarwal R and Mukhtar H . (1995). Photochem. Photobiol., 62, 855–861.

  • Katiyar SK, Korman NJ, Mukhtar H and Agarwal R . (1997). J. Natl. Cancer Inst., 89, 556–566.

  • Katiyar SK and Mukhtar H . (2001). J. Leukoc. Biol., 69, 719–726.

  • Katiyar SK, Perez A and Mukhtar H . (2000). Clin. Cancer Res., 6, 3864–3869.

  • Kaufman CK and Fuchs E . (2000). J. Cell Biol., 149, 999–1004.

  • Kim J, Hwang JS, Cho YK, Han Y, Jeon YJ and Yang KH . (2001). Skin Pharmacol. Appl. Skin Physiol., 14, 11–19.

  • Kyriakis JM and Avruch J . (2001). Physiol. Rev., 81, 807–869.

  • Learn DB, Beard J and Moloney SJ . (1993). Photodermatol. Photoimmunol. Photomed., 9, 147–153.

  • Lefort K, Rouault JP, Tondereau L, Magaud JP and Dore JF . (2001). Oncogene, 20, 7375–7385.

  • Maniatis T . (1997). Science, 278, 818–819.

  • Milne DM, Campbell LE, Campbell DG and Meek DW . (1995). J. Biol. Chem., 270, 5511–5518.

  • Mittal A, Elmets CA and Katiyar SK . (2003). Carcinogenesis, 24, 1379–1388.

  • Mukhtar H and Elmets CA . (1996). Photochem. Photobiol., 63, 356–357.

  • Nghiem DX, Kazimi N, Mitchell DL, Vink AA, Ananthaswamy HN, Kripke ML and Ullrich SE . (2002). J. Invest. Dermatol., 119, 600–608.

  • Nomura M, Kaji A, He Z, Ma WY, Miyamoto K, Yang CS and Dong Z . (2001). J. Biol. Chem., 276, 46624–46631.

  • Potapova O, Gorospe M, Bost F, Dean NM, Gaarde WA, Mercola D and Holbrook NJ . (2000). J. Biol. Chem., 275, 24767–24775.

  • Potapova O, Basu S, Mercola D and Holbrook NJ . (2001). J. Biol. Chem., 276, 28546–28553.

  • Read MA, Whitley MZ, Gupta S, Pierce JW, Best J, Davis RJ and Collins T . (1997). J. Biol. Chem., 272, 2753–2761.

  • Scharffetter–kochanek K, Wlaschek M, Brenneisen P, Schauen M, Bladschun R and Wenk J . (1997). Biol. Chem., 378, 1247–1257.

  • She QB, Ma WY, Zhong S and Dong Z . (2002). J. Biol. Chem., 277, 24039–24048.

  • Stahl W and Sies H . (2002). Skin Pharmacol. Appl. Skin Physiol., 15, 291–296.

  • Su B and Karin M . (1996). Curr. Opin. Immunol., 8, 402–411.

  • Thanos AM and Maniatis T . (1995). Cell, 80, 529–532.

  • Vink AA, Moodycliffe AM, Shreedhar V, Ullrich SE, Roza L, Yarosh DB and Kripke ML . (1997). Proc. Natl. Acad. Sci. USA, 94, 5255–5260.

  • Wang ZY, Agarwal R, Bickers DR and Mukhtar H . (1991). Carcinogenesis, 12, 1527–1530.

  • Xia Z, Dickens M, Raingeaud J, Davis RJ and Greenberg ME . (1995). Science, 270, 1326–13231.

  • Yamazaki S, Muta T and Takeshige K . (2001). J. Biol. Chem., 276, 27657–27662.

  • Yang CS, Maliakal P and Meng X . (2002). Annu. Rev. Pharmacol. Toxicol., 42, 25–54.

  • Zhu WH, MacIntyre A and Nicosia RF . (2002). Am. J. Pathol., 161, 823–830.

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  1. Department of Dermatology, University of Wisconsin, Madison, 53706, WI, USA

    Farrukh Afaq, Nihal Ahmad & Hasan Mukhtar

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  1. Farrukh Afaq
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Correspondence to Hasan Mukhtar.

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Afaq, F., Ahmad, N. & Mukhtar, H. Suppression of UVB-induced phosphorylation of mitogen-activated protein kinases and nuclear factor kappa B by green tea polyphenol in SKH-1 hairless mice. Oncogene 22, 9254–9264 (2003). https://doi.org/10.1038/sj.onc.1207035

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