Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease that is associated with Th2 cell-mediated allergy. The process that leads to infiltration of inflammatory cells into an AD lesion is remarkably dependent on various chemokines, especially TARC (thymus and activation-regulated c...
Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease that is associated with Th2 cell-mediated allergy. The process that leads to infiltration of inflammatory cells into an AD lesion is remarkably dependent on various chemokines, especially TARC (thymus and activation-regulated chemokine/CCL17) and MDC (macrophage-derived chemokine/CCL22). Serum levels of these chemokines are over-expressed in AD patients. Citrus unshiu, which is known as Satsuma mandarin, has anti-oxidative, anti-inflammation, and anti-microviral activity. Therefore, we investigated the effect of EtOH extract of premature C. unshiu on AD. We did this using a DNCB-induced AD mouse model. We also tried to confirm an inhibitory effect for premature C. unshiu on the expression of inflammatory chemokines in IFN-${\gamma}$ and TNF-${\alpha}$ stimulated HaCaT human keratinocytes. We found that extract of premature C. unshiu reduced DNCB-induced symptoms such as hyperkeratosis, increased skin thickness, and infiltrated mast cells, in our AD-like animal model. The extract decreased levels of IFN-${\gamma}$ and IL-4 in ConA-stimulated splenocytes isolated from DNCB-treated mice. Also, extract of premature C. unshiu inhibited mRNA expression and protein production of TARC and MDC through the inhibition of STAT1 phosphorylation. These results suggest that C. unshiu has anti-atopic activity by regulating inflammatory chemokines such as TARC and MDC.
Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease that is associated with Th2 cell-mediated allergy. The process that leads to infiltration of inflammatory cells into an AD lesion is remarkably dependent on various chemokines, especially TARC (thymus and activation-regulated chemokine/CCL17) and MDC (macrophage-derived chemokine/CCL22). Serum levels of these chemokines are over-expressed in AD patients. Citrus unshiu, which is known as Satsuma mandarin, has anti-oxidative, anti-inflammation, and anti-microviral activity. Therefore, we investigated the effect of EtOH extract of premature C. unshiu on AD. We did this using a DNCB-induced AD mouse model. We also tried to confirm an inhibitory effect for premature C. unshiu on the expression of inflammatory chemokines in IFN-${\gamma}$ and TNF-${\alpha}$ stimulated HaCaT human keratinocytes. We found that extract of premature C. unshiu reduced DNCB-induced symptoms such as hyperkeratosis, increased skin thickness, and infiltrated mast cells, in our AD-like animal model. The extract decreased levels of IFN-${\gamma}$ and IL-4 in ConA-stimulated splenocytes isolated from DNCB-treated mice. Also, extract of premature C. unshiu inhibited mRNA expression and protein production of TARC and MDC through the inhibition of STAT1 phosphorylation. These results suggest that C. unshiu has anti-atopic activity by regulating inflammatory chemokines such as TARC and MDC.
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제안 방법
unshiu reduced the production of Th1 and Th2 cytokines by splenocytes from DNCB-challenged mice. Next, we analyzed the effect of premature C. unshiu on the production of cytokines induced by modulation of the Th1 and Th2 cytokine milieu in splenocytes isolated from DNCB-challenged mice. In the presence of ConA, levels of IL-4 (22.
To identify the effect of premature C. unshiu on cell viability in IFN-γ and TNF-α stimulated HaCaT human keratinocytes, cell viability was examined using MTT assay.
대상 데이터
Female, 7-week-old SKH1-hairless mice (25 ± 2 g) were purchased from Orient Bio (Korea) and were maintained for 1 week before the start of any experiments.
Fetal bovine serum (FBS), Dulbecco’s modified Eagle’s medium (DMEM), and RPMI1640 were obtained from GIBCO.
데이터처리
Student’s t-test and two-way analysis of variance were used to determine the statistical significance of differences between values for the experimental and control groups.
이론/모형
Cells were then stimulated with IFN-γ (10 ng/ml) and TNF-α (10 ng/ml) in the presence of premature CU (25, 50, 100, or 200 µg/ml) for 24 hr. Cell viability was analyzed by MTT assay. The error bars indicate standard deviation.
Cell viability assay. Cell viability was determained using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assays. Briefly, HaCaT cells were stimulated with IFN-γ and TNF-α in the absence or presence of extract of premature C.
The cell lysates were centrifuged at 15,000 rpm for 15 min at 4℃ and supernatants were used for western blotting. Total protein concentration of each sample was quantified by the BioRad assay method (Bio-Rad, Hercules, CA). Extracts con taining 30 µg of protein were separated on an 8% sodium dodecylsulfate (SDS) polyacrylamide gel and transferred onto a polyvinylidene fluoride (PVDF) membrane.
후속연구
However, further investigation is needed to determine whether the inhibitory effect of premature C. unshiu on STAT1 phosphorylation occurs through inhibition of Jak1/2 or through effects on other pathway components such as ERK, p38, and NF-κB.
참고문헌 (28)
1 Abramovits W. Atopic dermatitis. J. Am. Acad. Dermatol. (2005) 53 S86 93 10.1016/j.jaad.2005.04.034 15968268
3 Choi I.Y. Kim S.J. Jeong H.J. Park S.H. Song Y.S. Lee J.H. Kang T.H. Park J.H. Hwang G.S. Lee E.J. Hong S.H. Kim H.M. Um J.Y. Hesperidin inhibits expression of hypoxia inducible factor-1 alpha and inflammatory cytokine production from mast cells. Mol. Cell Biochem. (2007) 305 153 161 10.1007/s11010-007-9539-x 17629775
6 Hijnen D. De Bruin-Weller M. Oosting B. Lebre C. De Jong E. Bruijnzeel-Koomen C. Knol E. Serum thymus and activation-regulated chemokine (TARC) and cutaneous T cell- attracting chemokine (CTACK) levels in allergic diseases: TARC and CTACK are disease-specific markers for atopic dermatitis. J. Allergy Clin. Immunol. (2004) 113 334 340 10.1016/j.jaci.2003.12.007 14767451
7 Imai T. Nagira M. Takagi S. Kakizaki M. Nishimura M. Wang J. Gray P.W. Matsushima K. Yoshie O. Selective recruitment of CCR4-bearing Th2 cells toward antigen- presenting cells by the CC chemokines thymus and activation- regulated chemokine and macrophage-derived chemokine. Int. Immunol. (1999) 11 81 88 10.1093/intimm/11.1.81 10050676
8 Itoh K. Masuda M. Naruto S. Murata K. Matsuda H. Antiallergic activity of unripe Citrus hassaku fruits extract and its flavanone glycosides on chemical substanceinduced dermatitis in mice. J. Nat. Med. (2009) 63 443 450 10.1007/s11418-009-0349-1 19603253
10 Ju S.M. Song H.Y. Lee S.J. Seo W.Y. Sin D.H. Goh A.R. Kang Y.H. Kang I.J. Won M.H. Yi J.S. Kwon D.J. Bae Y.S. Choi S.Y. Park J. Suppression of thymusand activation-regulated chemokine (TARC/CCL17) production by 1,2,3,4,6-penta-O-galloyl-beta-D-glucose via blockade of NF-kappaB and STAT1 activation in the HaCaT cells. Biochem. Biophys. Res. Commun. (2009) 387 115 120 10.1016/j.bbrc.2009.06.137 19576177
11 Kakinuma T. Nakamura K. Wakugawa M. Mitsui H. Tada Y. Saeki H. Torii H. Komine M. Asahina A. Tamaki K. Serum macrophage-derived chemokine (MDC) levels are closely related with the disease activity of atopic dermatitis. Clin. Exp. Immunol. (2002) 127 270 273 10.1046/j.1365-2249.2002.01727.x 11876749
12 Kang Y.J. Yang M.H. Ko W.J. Park S.R. Lee B.G. Studies on the major components and antioxidative properties of whole fruit powder and juice prepared from premature mandarin orange. Korean J. Food Sci. Technol. (2005) 37 783 788
13 Kim Y.D. Mahinda S. Koh K.S. Jeon Y.J. Kim S.H. Reactive Oxygen Species Scavenging Activity of Jeju Native Citrus Peel during Maturation. J. Korean Soc. Food Sci. Nutr. (2009) 38 462 469 10.3746/jkfn.2009.38.4.462
14 Kitagaki H. Fujisawa S. Watanabe K. Hayakawa K. Shiohara T. Immediate-type hypersensitivity response followed by a late reaction is induced by repeated epicutaneous application of contact sensitizing agents in mice. J. Invest. Dermatol. (1995) 105 749 755 10.1111/1523-1747.ep12325538 7490467
16 Lee S.H. Heo Y. Kim Y.C. Effect of German chamomile oil application on alleviating atopic dermatitis-like immune alterations in mice. J. Vet. Sci. (2010) 11 35 41 10.4142/jvs.2010.11.1.35 20195063
17 Leung T.F. Ma K.C. Hon K.L. Lam C.W. Wan H. Li C.Y. Chan I.H. Serum concentration of macrophagederived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young children. Pediatr. Allergy Immunol. (2003) 14 296 301 10.1034/j.1399-3038.2003.00052.x 12911508
18 Matsumoto K. Mizukoshi K. Oyobikawa M. Ohshima H. Sakai Y. Tagami H. Objective evaluation of the efficacy of daily topical applications of cosmetics bases using the hairless mouse model of atopic dermatitis. Skin Res. Technol. (2005) 11 209 217 10.1111/j.1600-0846.2005.00106.x 15998334
19 Matsumoto K. Mizukoshi K. Oyobikawa M. Ohshima H. Tagami H. Establishment of an atopic dermatitis-like skin model in a hairless mouse by repeated elicitation of contact hypersensitivity that enables to conduct functional analyses of the stratum corneum with various non-invasive biophysical instruments. Skin Res. Technol. (2004) 10 122 129 10.1111/j.1600-0846.2004.00062.x 15059180
20 Murakami A. Nakamura Y. Torikai K. Tanaka T. Koshiba T. Koshimizu K. Kuwahara S. Takahashi Y. Ogawa K. Yano M. Tokuda H. Nishino H. Mimaki Y. Sashida Y. Kitanaka S. Ohigashi H. Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice. Cancer Res. (2000) 60 5059 5066 11016629
21 Nakazato J. Kishida M. Kuroiwa R. Fujiwara J. Shimoda M. Shinomiya N. Serum levels of Th2 chemokines, CCL17, CCL22, and CCL27, were the important markers of severity in infantile atopic dermatitis. Pediatr. Allergy Immunol. (2008) 19 605 613 18266834
22 Pease J.E. Williams T.J. Chemokines and their receptors in allergic disease. J. Allergy Clin. Immunol. (2006) 118 305 318 10.1016/j.jaci.2006.06.010 16890751
23 Qi X.F. Kim D.H. Yoon Y.S. Li J.H. Jin D. Deung Y.K. Lee K.J. Effects of Bambusae caulis in Liquamen on the development of atopic dermatitis-like skin lesions in hairless mice. J. Ethnopharmacol. (2009) 123 195 200 19429362
24 Qi X.F. Teng Y.C. Yoon Y.S. Kim D.H. Cai D.Q. Lee K.J. Reactive oxygen species are involved in the IFNgamma- stimulated production of Th2 chemokines in HaCaT keratinocytes. J. Cell Physiol. (2011) 226 58 65 10.1002/jcp.22303 20625996
25 Saha B. Jyothi Prasanna S. Chandrasekar B. Nandi D. Gene modulation and immunoregulatory roles of interferon gamma. Cytokine. (2010) 50 1 14 10.1016/j.cyto.2009.11.021 20036577
26 Sakata K. Hirose Y. Qiao Z. Tanaka T. Mori H. Inhibition of inducible isoforms of cyclooxygenase and nitric oxide synthase by flavonoid hesperidin in mouse macrophage cell line. Cancer Lett. (2003) 199 139 145 10.1016/S0304-3835(03)00386-0 12969786
27 Vestergaard C. Yoneyama H. Murai M. Nakamura K. Tamaki K. Terashima Y. Imai T. Yoshie O. Irimura T. Mizutani H. Matsushima K. Overproduction of Th2-specific chemokines in NC/Nga mice exhibiting atopic dermatitis-like lesions. J. Clin. Invest. (1999) 104 1097 1105 10.1172/JCI7613 10525048
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