BMC Complementary and Alternative Medicine | |
Modulation of experimental atopic dermatitis by topical application of Gami-Cheongyeul-Sodok-Eum | |
Sin-Hyeog Im2  Young-Beob Yu1  Jung-Eun Kim2  Ji Sun Hwang2  | |
[1] Department of Herbal Pharmaceutical Development, Nambu University, 23, Cheomdan-jungangro, Gwangsan-gu, Gwangju 506-706, Republic of Korea;School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea | |
关键词: IgE and Cytokines; B cells; Th2 cells; Th1 & GCSE (Gami-Cheongyeul-Sodok-Eum); Herbal medicine; Atopic dermatitis; | |
Others : 1220803 DOI : 10.1186/1472-6882-13-312 |
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received in 2013-10-26, accepted in 2013-11-01, 发布年份 2013 | |
【 摘 要 】
Background
Gami-Cheongyeul-Sodok-Eum (GCSE), an herbal formula of traditional Korean medicine, comprises nine herb components. GCSE has various biological activities such as anti-inflammatory, anti-bacterial and anti-viral activities. However, it is still unclear whether GCSE has any immunomodulatory effect on atopic dermatitis (AD).
Methods
GCSE was treated to primary B cells and CD4+ T cells isolated from atopic mice to compare its inhibitory effects on IgE secretion and cytokine expression. Experimental AD was established by alternative treatment of 2, 4-dinitrochlorobenzene (DNCB) and house dust mite extract to the ears of BALB/c mice. GCSE was topically applied to ears of atopic mice every day for 3 weeks. AD progression was analyzed by measuring ear thickness, serum IgE level, histological examination of ear tissue by H&E staining and cytokine profile of CD4+ T cells and CD19+ B cells by real time PCR and ELISA.
Results
Treatment of GCSE significantly reduced IgE production and expression of AD associated pathogenic cytokines such as IL-4, IL-5, IL-10, IL-13, IL-17, TNF-α, and IFN-γ by lymphocytes isolated from AD-induced mice. Topical application of GCSE on the ears of AD-induced mice significantly reduced ear thickness, clinical score and lymphocytes infiltration to ears as compared to control group. GCSE treatment also reduced serum IgE level and the levels of major pathogenic cytokines such as IL-4, IL-5, IL-10, IL-13 and IL-17. In addition, GCSE treatment significantly increased Foxp3 expression level.
Conclusions
The protective effect of GCSE in experimental AD is mediated by inhibition of IgE production, by reduction in the levels of pathogenic cytokines and by induction of Foxp3, all of which are suggesting the beneficial effect of GCSE on modulating atopic dermatitis.
【 授权许可】
2013 Hwang et al.; licensee BioMed Central Ltd.
【 预 览 】
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Figure 1. | 58KB | Image | download |
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【 参考文献 】
- [1]Leung DYM, Jain N, Leo HL: New concepts in the pathogenesis of atopic dermatitis. Curr Opin Immunol 2003, 15(6):634-638.
- [2]Boguniewicz M, Leung DYM: Recent insights into atopic dermatitis and implications for management of infectious complications. J Allergy Clin Immunol 2011, 125(1):4-13.
- [3]Kupper TS, Fuhlbrigge RC: Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol 2004, 4(3):211-222.
- [4]De Benedetto A, Agnihothri R, McGirt LY, Bankova LG, Beck LA: Atopic dermatitis: a disease caused by innate immune defects [quest]. J Invest Dermatol 2009, 129(1):14-30.
- [5]Leung DYM: Atopic dermatitis: The skin as a window into the pathogenesis of chronic allergic diseases. J Allergy Clin Immunol 1995, 96(3):302-319.
- [6]Chen L, Martinez O, Overbergh L, Mathieu C, Prabhakar BS, Chan LS: Early up-regulation of Th2 cytokines and late surge of Th1 cytokines in an atopic dermatitis model. Clin Exp Immunol 2004, 138(3):375-387.
- [7]Lee H-J, Lee H-P, Ha S-J, Byun D-G, Kim J-W: Spontaneous expression of mRNA for IL-10, GM-CSF, TGF-[beta], TNF-[alpha], and IL-6 in peripheral blood mononuclear cells from atopic dermatitis. Ann Allergy Asthma Immunol 2000, 84(5):553-558.
- [8]Tazawa T, Sugiura H, Sugiura Y, Uehara M: Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis. Arch Dermatol Res 2004, 295(11):459-464.
- [9]Bruynzeel-Koomen C, Wichen DF, Toonstra J, Berrens L, Bruynzeel PLB: The presence of IgE molecules on epidermal langerhans cells in patients with atopic dermatitis. Arch Dermatol Res 1986, 278(3):199-205.
- [10]Hajoui O, Janani R, Tulic M, Joubert P, Ronis T, Hamid Q, Zheng H, Mazer BD: Synthesis of IL-13 by human B lymphocytes: regulation and role in IgE production. J Allergy Clin Immunol 2004, 114(3):657-663.
- [11]Vestergaard C, Kirstejn N, Gesser B, Mortensen JT, Matsushima K, Larsen CG: IL-10 augments the IFN-[gamma] and TNF-[alpha] induced TARC production in HaCaT cells: a possible mechanism in the inflammatory reaction of atopic dermatitis. J Dermatol Sci 2001, 26(1):46-54.
- [12]Leung DYM, Boguniewicz M, Howell MD, Nomura I, Hamid QA: New insights into atopic dermatitis. J Clin Invest 2004, 113(5):651-657.
- [13]Konur A, Schulz U, Eissner G, Andreesen R, Holler E: Interferon (IFN)-γ is a main mediator of keratinocyte (HaCaT) apoptosis and contributes to autocrine IFN-γ and tumour necrosis factor-α production. Br J Dermatol 2005, 152(6):1134-1142.
- [14]Richardson MA, Sanders T, Palmer JL, Greisinger A, Singletary SE: Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology. J Clin Oncol 2000, 18(13):2505-2514.
- [15]Lee K-H: Research and future trends in the pharmaceutical development of medicinal herbs from Chinese medicine. Public Health Nutr 2000, 3(4a):515-522.
- [16]Jeon B-H JW-Y: Influence of medicinal herba drug on the experimental model of thrombosis in animal. Kor J Orient Med Pathol 1996, 10(1):72-78.
- [17]Kim J-J KH-T: Effect of Chongyeal-sodok-yeum on chemokines expression in lung epithelial cells. J Korean Orient Med Ophthalmol Otolaryngol Dermatol 2006, 19(1):115-122.
- [18]Kim YW, Zhao RJ, Park SJ, Lee JR, Cho IJ, Yang CH, Kim SG, Kim SC: Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-κB-dependent iNOS and proinflammatory cytokines production. Br J Pharmacol 2008, 154(1):165-173.
- [19]Kim J-H, Jeong J-H, Jeon S-T, Kim H, Ock J, Suk K, Kim S-I, Song K-S, Lee W-h: Decursin inhibits induction of inflammatory mediators by blocking nuclear factor-kB activation in macrophages. Mol Pharmacol 2006, 69(6):1783-1790.
- [20]Ryu M, Kim EH, Chun M, Kang S, Shim B, Yu Y-B, Jeong G, Lee J-S: Astragali Radix elicits anti-inflammation via activation of MKP-1, concomitant with attenuation of p38 and Erk. J Ethnopharmacol 2008, 115(2):184-193.
- [21]Kwon H-K, Lee C-G, So J-S, Chae C-S, Hwang J-S, Sahoo A, Nam JH, Rhee JH, Hwang K-C, Im S-H: Generation of regulatory dendritic cells and CD4 + Foxp3+ T cells by probiotics administration suppresses immune disorders. Proc Natl Acad Sci 2010, 107(5):2159-2164.
- [22]Hwang JS, Kwon H-K, Kim J-E, Rho J, Im S-H: Immunomodulatory effect of water soluble extract separated from mycelium of Phellinus linteus on experimental atopic dermatitis. BMC Complement Altern Med 2012, 12(1):159. BioMed Central Full Text
- [23]Homey B, Steinhoff M, Ruzicka T, Leung DYM: Cytokines and chemokines orchestrate atopic skin inflammation. J Allergy Clin Immunol 2006, 118(1):178-189.
- [24]Son JS, Chae CS, Hwang JS, Park ZY, Im SH: Enhanced chromatin accessibility and recruitment of JUNB mediate the sustained IL-4 expression in NFAT1 deficient T helper 2 cells. PLoS One 2011, 6(7):e22042.
- [25]Hwang JS, Kim JE, Kim HT, Yu YB, Im SH: Topical application of Taglisodog-eum inhibits the development of experimental atopic dermatitis. J Ethnopharmacol 2012, 145(2):536-546.
- [26]M-J O, Yoo Y-B, Lim S-H, Kim H-T: A clinical study for the effect of ointment contained Takrisodok-Eum on recovering the damaged skin barrier by Atopic dermatitis. J Korean Orient Med Ophthalmol Otolaryngol Dermatol 2011, 24(3):84-107.
- [27]An B-J LJ-T, Lee C-E, Son J-H, Lee J-Y, Park T-S, Lee I-C, Song M-A, Cheon S-J, Jee S-Y: Cytotoxicity, antibacterial and antioxidant activities of the prescription Cheongyeolsodokum and its constituent herbs. Kor J Herbology 2005, 20(4):41-51.
- [28]H-M K: Effect of Chongyealsodokyeum on the experimental inflammation and thrombosis. J Orient Med Pathol 1995, 10:267-293.
- [29]Schröfelbauer BRJ, Hauner M, Wolkerstorfer A, Ernst W, Szolar OHJ: Glycyrrhizin, the main active compound in liquorice, attenuates pro-inflammatory responses by interfering with membrane-dependent receptor signalling. Biochem J 2009, 421(3):473-482.
- [30]Kang HS, Lee JY, Kim CJ: Anti-inflammatory activity of arctigenin from Forsythiae Fructus. J Ethnopharmacol 2008, 116(2):305-312.
- [31]Akdis CA, Akdis M, Bieber T, Bindslev-Jensen C, Boguniewicz M, Eigenmann P, Hamid Q, Kapp A, Leung DYM, Lipozencic J, et al.: Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report. J Allergy Clin Immunol 2006, 118(1):152-169.
- [32]Cookson W: The immunogenetics of asthma and eczema: a new focus on the epithelium. Nat Rev Immunol 2004, 4(12):978-988.
- [33]Wollenberg A, Bieber T: Atopic dermatitis: from the genes to skin lesions. Allergy 2000, 55(3):205-213.
- [34]Padilla J, Daley E, Chow A, Robinson K, Parthasarathi K, McKenzie ANJ, Tschernig T, Kurup VP, Donaldson DD, Grunig G: IL-13 Regulates the Immune Response to Inhaled Antigens. J Immunol 2005, 174(12):8097-8105.
- [35]Fujisawa T, Fujisawa R, Kato Y, Nakayama T, Morita A, Katsumata H, Nishimori H, Iguchi K, Kamiya H, Gray PW, et al.: Presence of high contents of thymus and activation-regulated chemokine in platelets and elevated plasma levels of thymus and activation-regulated chemokine and macrophage-derived chemokine in patients with atopic dermatitis. J Allergy Clin Immunol 2002, 110(1):139-146.
- [36]Jahnz-Rozyk K, Targowski T, Paluchowska E, Owczarek W, Kucharczyk A: Serum thymus and activation-regulated chemokine, macrophage-derived chemokine and eotaxin as markers of severity of atopic dermatitis. Allergy 2005, 60(5):685-688.
- [37]Kolls JK: Oxidative stress in sepsis: a redox redux. J Clin Invest 2006, 116(4):860-863.
- [38]Nakae S, Komiyama Y, Nambu A, Sudo K, Iwase M, Homma I, Sekikawa K, Asano M, Iwakura Y: Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity 2002, 17(3):375-387.
- [39]Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, Donaldson DD: Interleukin-13: Central mediator of allergic asthma. Science 1998, 282(5397):2258-2261.
- [40]Kabesch M, Schedel M, Carr D, Woitsch B, Fritzsch C, Weiland SK, von Mutius E: IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood asthma. J Allergy Clin Immunol 2006, 117(2):269-274.
- [41]Ziegler SF: FOXP3: of mice and men. Annu Rev Immunol 2006, 24(1):209-226.