Activation of the HMGB1‑TLR4‑NF‑κB pathway may occur in patients with atopic eczema

Wang,Yong; Weng,Hui; Song,Jian Fei; Deng,Yun Hua; Li,Shuang; Liu,Hong Bo

doi:10.3892/mmr.2017.6942

Activation of the HMGB1‑TLR4‑NF‑κB pathway may occur in patients with atopic eczema

Authors:
- Yong Wang
- Hui Weng
- Jian Fei Song
- Yun Hua Deng
- Shuang Li
- Hong Bo Liu
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Affiliations: Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, P.R. China, Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, P.R. China, Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Clinical Laboratory, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, Guangxi 541002, P.R. China
Published online on: July 6, 2017 https://doi.org/10.3892/mmr.2017.6942
Pages: 2714-2720
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

High mobility group protein B1 (HMGB1) has been reported to serve important roles in various pathological conditions. Toll‑like receptor 4 (TLR4), as one of the HMGB1 receptors, has been reported to be involved in the development of certain inflammatory diseases by activating nuclear factor NF‑κ‑B (NF‑κB). However, there are few studies investigating the effects of HMGB1, TLR4 and NF‑κB on human inflammatory dermatoses. In the present study, the distribution and characteristics of HMGB1, TLR4 and NF‑κB p65 expression in psoriasis and atopic eczema (AE) were investigated. In addition, immunohistochemical analysis was performed to evaluate their expression and distribution in normal skin, and in patients with AE or psoriasis. Spearman's correlation analysis was used to predicate their relevancy. The present study identified that the p65 level in epithelial nuclei in AE skin was increased compared with normal and psoriasis skin (P<0.01). The level of extracellular HMGB1 in AE skin was also increased compared with normal and psoriasis skin (P<0.01). Meanwhile, TLR4 expression on the epithelial membranes of AE skin was increased compared with psoriasis skin (P<0.01). Furthermore, the level of extracellular HMGB1 was positively correlated with epithelial membrane TLR4 (r=0.3856; P<0.05) and epithelial nuclear p65 (r=0.5894; P<0.01) in AE skin. These results indicated that the HMGB1‑TLR4‑NF‑κB signaling pathway is activated in AE and may account for its pathogenesis, but not in psoriasis. Therefore, HMGB1, TLR4 and NF‑κB p65 have the potential to be targets for the treatment of human inflammatory dermatoses, including AE.

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1	Hanifin JM: Evolving concepts of pathogenesis in atopic dermatitis and other eczemas. J Invest Dermatol. 129:320–322. 2009. View Article : Google Scholar : PubMed/NCBI
2	Werfel T, Breuer K, Ruéff F, Przybilla B, Worm M, Grewe M, Ruzicka T, Brehler R, Wolf H, Schnitker J and Kapp A: Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: A multi-centre, randomized, dose-response study. Allergy. 61:202–205. 2006. View Article : Google Scholar : PubMed/NCBI
3	Lowes MA, Bowcock AM and Krueger JG: Pathogenesis and therapy of psoriasis. Nature. 445:866–873. 2007. View Article : Google Scholar : PubMed/NCBI
4	Lew W, Bowcock AM and Krueger JG: Psoriasis vulgaris: Cutaneous lymphoid tissue supports T-cell activation and ‘Type 1’ inflammatory gene expression. Trends Immunol. 25:295–305. 2004. View Article : Google Scholar : PubMed/NCBI
5	Boyman O, Conrad C, Tonel G, Gilliet M and Nestle FO: The pathogenic role of tissue-resident immune cells in psoriasis. Trends Immunol. 28:51–57. 2007. View Article : Google Scholar : PubMed/NCBI
6	Griffiths CE and Barker JN: Pathogenesis and clinical features of psoriasis. Lancet. 370:263–271. 2007. View Article : Google Scholar : PubMed/NCBI
7	Boniface K, Guignouard E, Pedretti N, Garcia M, Delwail A, Bernard FX, Nau F, Guillet G, Dagregorio G, Yssel H, et al: A role for T cell-derived interleukin 22 in psoriatic skin inflammation. Clin Exp Immunol. 150:407–415. 2007. View Article : Google Scholar : PubMed/NCBI
8	Takahashi H, Tsuji H, Hashimoto Y, Ishida-Yamamoto A and Iizuka H: Serum cytokines and growth factor levels in Japanese patients with psoriasis. Clin Exp Dermatol. 35:645–649. 2010. View Article : Google Scholar : PubMed/NCBI
9	Kasraie S and Werfel T: Role of macrophages in the pathogenesis of atopic dermatitis. Mediators Inflamm. 2013:9423752013. View Article : Google Scholar : PubMed/NCBI
10	Valledor AF, Comalada M, Santamaria-Babi LF, Lloberas J and Celada A: Macrophage proinflammatory activation and deactivation: A question of balance. Adv Immunol. 108:1–20. 2010. View Article : Google Scholar : PubMed/NCBI
11	Dai S, Sodhi C, Cetin S, Richardson W, Branca M, Neal MD, Prindle T, Ma C, Shapiro RA, Li B, et al: Extracellular high mobility group box-1 (HMGB1) inhibits enterocyte migration via activation of Toll-like receptor-4 and increased cell-matrix adhesiveness. J Biol Chem. 285:4995–5002. 2010. View Article : Google Scholar : PubMed/NCBI
12	Pisetsky D: Cell death in the pathogenesis of immune-mediated diseases: The role of HMGB1 and DAMP-PAMP complexes. Swiss Med Wkly. 141:w132562011.PubMed/NCBI
13	Tadie JM, Bae HB, Deshane JS, Bell CP, Lazarowski ER, Chaplin DD, Thannickal VJ, Abraham E and Zmijewski JW: Toll-like receptor 4 engagement inhibits adenosine 5′-monophosphate-activated protein kinase activation through a high mobility group box 1 protein-dependent mechanism. Mol Med. 18:659–668. 2012. View Article : Google Scholar : PubMed/NCBI
14	Oh H and Ghosh S: NF-κB: Roles and regulation in different CD4(+) T-cell subsets. Immunol Rev. 252:41–51. 2013. View Article : Google Scholar : PubMed/NCBI
15	Harris HE, Andersson U and Pisetsky DS: HMGB1: A multifunctional alarmin driving autoimmune and inflammatory disease. Nat Rev Rheumatol. 8:195–202. 2012. View Article : Google Scholar : PubMed/NCBI
16	Weng H, Deng Y, Xie Y, Liu H and Gong F: Expression and significance of HMGB1, TLR4 and NF-κB p65 in human epidermal tumors. Bmc Cancer. 13:3112013. View Article : Google Scholar : PubMed/NCBI
17	Chen T, Guo ZP, Li L, Wang L, Jia RZ, Cao N, Qin S and Li MM: Increased HMGB1 serum levels and altered HMGB1 expression in patients with psoriasis vulgaris. Arch Dermatol Res. 305:263–267. 2013. View Article : Google Scholar : PubMed/NCBI
18	Nakajima S, Watanabe H, Tohyama M, Sugita K, Iijima M, Hashimoto K, Tokura Y, Nishimura Y, Doi H, Tanioka M, et al: High-mobility group box 1 protein (HMGB1) as a novel diagnostic tool for toxic epidermal necrolysis and Stevens-Johnson syndrome. Arch Dermatol. 147:1110–1112. 2011. View Article : Google Scholar : PubMed/NCBI
19	Oranje AP, Glazenburg EJ, Wolkerstorfer A and de Waard-van der Spek FB: Practical issues on interpretation of scoring atopic dermatitis: The SCORAD index, objective SCORAD and the three-item severity score. Br J Dermatol. 157:645–648. 2007. View Article : Google Scholar : PubMed/NCBI
20	Langley RG and Ellis CN: Evaluating psoriasis with psoriasis area and severity index, psoriasis global assessment, and lattice system physician's global assessment. J Am Acad Dermatol. 51:563–569. 2004. View Article : Google Scholar : PubMed/NCBI
21	Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D and Miyamoto S: Rel/NF-kappa B/I kappa B family: Intimate tales of association and dissociation. Genes Dev. 9:2723–2735. 1995. View Article : Google Scholar : PubMed/NCBI
22	Ghosh S, May MJ and Kopp EB: NF-kappa B and Rel proteins: Evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 16:225–260. 1998. View Article : Google Scholar : PubMed/NCBI
23	Li Q and Verma IM: NF-kappaB regulation in the immune system. Nat Rev Immunol. 2:725–734. 2002. View Article : Google Scholar : PubMed/NCBI
24	Mayo MW and Baldwin AS: The transcription factor NF-kappaB: Control of oncogenesis and cancer therapy resistance. Biochim Biophys Acta. 1470:M55–M62. 2000.PubMed/NCBI
25	Lin A and Karin M: NF-kappaB in cancer: A marked target. Semin Cancer Biol. 13:107–114. 2003. View Article : Google Scholar : PubMed/NCBI
26	Karuppagounder V, Arumugam S, Thandavarayan RA, Pitchaimani V, Sreedhar R, Afrin R, Harima M, Suzuki H, Nomoto M, Miyashita S, et al: Modulation of HMGB1 translocation and RAGE/NFκB cascade by quercetin treatment mitigates atopic dermatitis in NC/Nga transgenic mice. Exp Dermatol. 24:418–423. 2015. View Article : Google Scholar : PubMed/NCBI
27	Lee HK, Kim HS, Kim YJ, Kim JS, Park YS, Kang JS, Yuk DY, Hong JT, Kim Y and Han SB: Sophoricoside isolated from Sophora japonica ameliorates contact dermatitis by inhibiting NF-κB signaling in B cells. Int Immunopharmacol. 15:467–473. 2013. View Article : Google Scholar : PubMed/NCBI
28	Kim JH, Kim MH, Yang G, Huh Y, Kim SH and Yang WM: Effects of topical application of Astragalus membranaceus on allergic dermatitis. Immunopharmacol Immunotoxicol. 35:151–156. 2013. View Article : Google Scholar : PubMed/NCBI
29	Goldminz AM, Au SC, Kim N, Gottlieb AB and Lizzul PF: NF-κB: An essential transcription factor in psoriasis. J Dermatol Sci. 69:89–94. 2013. View Article : Google Scholar : PubMed/NCBI
30	Yan S, Xu Z, Lou F, Zhang L, Ke F, Bai J, Liu Z, Liu J, Wang H, Zhu H, et al: NF-κB-induced microRNA-31 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis. Nat Commun. 6:76522015. View Article : Google Scholar : PubMed/NCBI
31	Andrés RM, Montesinos MC, Navalón P, Payá M and Terencio MC: NF-κB and STAT3 inhibition as a therapeutic strategy in psoriasis: In vitro and in vivo effects of BTH. J Invest Dermatol. 133:2362–2371. 2013. View Article : Google Scholar : PubMed/NCBI
32	Kaisho T and Akira S: Toll-like receptor function and signaling. J Allergy Clin Immunol. 117:979–987; quiz 988. 2006. View Article : Google Scholar : PubMed/NCBI
33	Park JS, Gamboni-Robertson F, He Q, Svetkauskaite D, Kim JY, Strassheim D, Sohn JW, Yamada S, Maruyama I, Banerjee A, et al: High mobility group box 1 protein interacts with multiple Toll-like receptors. Am J Physiol Cell Physiol. 290:C917–C924. 2006. View Article : Google Scholar : PubMed/NCBI
34	Nair AR, Ebenezer PJ, Saini Y and Francis J: Angiotensin II-induced hypertensive renal inflammation is mediated through HMGB1-TLR4 signaling in rat tubulo-epithelial cells. Exp Cell Res. 335:238–247. 2015. View Article : Google Scholar : PubMed/NCBI
35	Wang FC, Pei JX, Zhu J, Zhou NJ, Liu DS, Xiong HF, Liu XQ, Lin DJ and Xie Y: Overexpression of HMGB1 A-box reduced lipopolysaccharide-induced intestinal inflammation via HMGB1/TLR4 signaling in vitro. World J Gastroenterol. 21:7764–7776. 2015. View Article : Google Scholar : PubMed/NCBI
36	Yang Z, Deng Y, Su D, Tian J, Gao Y, He Z and Wang X: TLR4 as receptor for HMGB1-mediated acute lung injury after liver ischemia/reperfusion injury. Lab Invest. 93:792–800. 2013. View Article : Google Scholar : PubMed/NCBI
37	Panzer R, Blobel C, Fölster-Holst R and Proksch E: TLR2 and TLR4 expression in atopic dermatitis, contact dermatitis and psoriasis. Exp Dermatol. 23:364–366. 2014. View Article : Google Scholar : PubMed/NCBI