白细胞介素-36β对体外培养角质形成细胞炎症反应与分化的影响

doi:10.24920/003489

Abstract

Objective Psoriasis is an immune-mediated inflammatory disease. Despite advances in the study of its pathogenesis, the exact development mechanism of psoriasis remains to be fully elucidated. Hyperproliferative epidermis plays a crucial role in psoriasis. This study aimed to investigate the effects of interleukin-36β (IL-36β) on keratinocyte dysfunction in vitro.

Methods Human keratinocyte cell lines, HaCaT cells, were treated with 0 (control), 50 or 100 ng/ml IL-36β respectively for 24 h. Cell viability was determined with a cell counting kit-8 assay. Flow cytometry was used to assess the effects of IL-36β on apoptosis and cell cycle distribution. Expressions of the differentiation markers, such as keratin 10 and involucrin, were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR). Expressions of the inflammatory cytokines, IL-1β and IL-6 were tested by ELISA.

Results CCK8 assay showed the survival rate had no significant difference between the control and treated group (P > 0.05). Flow cytometry analysis showed cell cycle arrest at S phase in the IL-36β-treated groups compared with the control group (P < 0.05). RT-qPCR verified the decreased mRNA expressions of keratin 10 and involucrin in the IL-36β-treated groups compared with the negative control (P < 0.01). ELISA showed 100 ng/ml IL-36β enhanced levels of IL-1β and IL-6 in culture supernatants of HaCaT cells compared with the negative control (P < 0.05).

Conclusion Taken together, these findings suggest that IL-36β could induce cell cycle arrest at S phase, inhibit keratin 10 and involucrin expressions and promote inflammatory activity in HaCaT cell lines.

Key words: interleukin-36β;, psoriasis, keratinocytes, inflammatory activity, differentiation

Wang Wenming, Wu Chao, Yu Xiaoling, Jin Hongzhong. IL-36β Promotes Inflammatory Activity and Inhibits Differentiation of Keratinocytes In Vitro[J].Chinese Medical Sciences Journal, 2019, 34(3): 199-204.

Figures/Tables 2

References 38.

1.	Bebes A, Kovacs-Solyom F, Prihoda J , et al. Interleukin-1 receptors are differentially expressed in normal and psoriatic T cells. Mediators Inflamm 2014; 2014:472625. doi: 10.1155/2014/472625.
2.	Boehncke WH, Schon MP . Psoriasis. Lancet 2015; 386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7.
3.	Nestle FO, Kaplan DH, Barker J . Psoriasis. N Engl J Med 2009; 361(5):496-509. doi: 10.1056/NEJMra0804595.
4.	Lowes MA, Bowcock AM, Krueger JG . Pathogenesis and therapy of psoriasis. Nature 2007; 445(7130):866-73. doi: 10.1038/nature05663.
5.	Chamian F, Lowes MA, Lin SL , et al. Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris. Proc Natl Acad Sci U S A 2005; 102(6):2075-80. doi: 10.1073/pnas.0409569102.
6.	Sticherling M . Psoriasis and autoimmunity. Autoimmun Rev 2016; 15(12):1167-70. doi: 10.1016/j.autrev.2016.09.004.
7.	Sims JE, Smith DE . The IL-1 family: regulators of immunity. Nat Rev Immunol 2010; 10(2):89-102. doi: 10.1038/nri2691.
8.	Balato A, Schiattarella M, Lembo S , et al. Interleukin-1 family members are enhanced in psoriasis and suppressed by vitamin D and retinoic acid. Arch Dermatol Res 2013; 305(3):255-62. doi: 10.1007/s00403-013-1327-8. doi: 10.1007/s00403-013-1327-8
9.	Baliwag J, Barnes DH, Johnston A . Cytokines in psoriasis. Cytokine 2015; 73(2):342-50. doi: 10.1016/j.cyto.2014.12.014.
10.	Hahn M, Frey S, Hueber AJ . The novel interleukin-1 cytokine family members in inflammatory diseases. Curr Opin Rheumatol 2017; 29(2):208-13. doi: 10.1097/BOR.0000000000000361.
11.	Walsh PT, Fallon PG . The emergence of the IL-36 cytokine family as novel targets for inflammatory diseases. Ann N Y Acad Sci 2018; 1417(1):23-34. doi: 10.1111/nyas.13280.
12.	Balato A, Mattii M, Caiazzo G , et al. IL-36gamma is involved in psoriasis and allergic contact dermatitis. J Invest Dermatol 2016; 136(7):1520-3. doi: 10.1016/j.jid.2016.03.020.
13.	Foster AM, Baliwag J, Chen CS , et al. IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin. J Immunol 2014; 192(12):6053-61. doi: 10.4049/jimmunol.1301481.
14.	Johnston A, Xing X, Wolterink L , et al. IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis. J Allergy Clin Immunol 2017; 140(1):109-20. doi: 10.1016/j.jaci.2016.08.056.
15.	Johnston A, Xing X, Guzman AM , et al. IL-1F5, -F6, -F8, and -F9: a novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression. J Immunol 2011; 186(4):2613-22. doi: 10.4049/jimmunol.1003162.
16.	Sehat M, Talaei R, Dadgostar E , et al. Evaluating serum levels of IL-33, IL-36, IL-37 and gene expression of IL-37 in patients with psoriasis vulgaris. Iran J Allergy Asthma Immunol 2018; 17(2):179-87.
17.	Carrier Y, Ma HL, Ramon HE , et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. J Invest Dermatol 2011; 131(12):2428-37. doi: 10.1038/jid.2011.234. doi: 10.1038/jid.2011.234
18.	Boutet MA, Bart G, Penhoat M , et al. Distinct expression of interleukin (IL)-36alpha, beta and gamma, their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn’s disease. Clin Exp Immunol 2016; 184(2):159-73. doi: 10.1111/cei.12761.
19.	van Asseldonk EJ, Stienstra R, Koenen TB , et al. The effect of the interleukin-1 cytokine family members IL-1F6 and IL-1F8 on adipocyte differentiation. Obesity (Silver Spring) 2010; 18(11):2234-6. doi: 10.1038/oby.2010.55.
20.	Magne D, Palmer G, Barton JL , et al. The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes. Arthritis Res Ther 2006; 8(3):R80. doi: 10.1186/ar1946.
21.	Grossman RM, Krueger J, Yourish D , et al. Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes. Proc Natl Acad Sci U S A 1989; 86(16):6367-71. doi: 10.1073/pnas.86.16.6367.
22.	Tamilselvi E, Haripriya D, Hemamalini M , et al. Association of disease severity with IL-1 levels in methotrexate-treated psoriasis patients. Scand J Immunol 2013; 78(6):545-53. doi: 10.1111/sji.12117.
23.	Kim TJ, Kim TH, Lee HJ , et al. Interleukin 1 polymorphisms in patients with ankylosing spondylitis in Korea. J Rheumatol 2008; 35(8):1603-8.
24.	Gresnigt MS, van de Veerdonk FL . Biology of IL-36 cytokines and their role in disease. Semin Immunol 2013; 25(6):458-65. doi: 10.1016/j.smim.2013.11.003.
25.	Di Caprio R, Balato A, Caiazzo G , et al. IL-36 cytokines are increased in acne and hidradenitis suppurativa. Arch Dermatol Res 2017; 309(8):673-8. doi: 10.1007/s00403-017-1769-5.
26.	D’Erme AM, Wilsmann-Theis D, Wagenpfeil J , et al. IL-36gamma (IL-1F9) is a biomarker for psoriasis skin lesions. J Invest Dermatol 2015; 135(4):1025-32. doi: 10.1038/jid.2014.532.
27.	Sahle FF, Gebre-Mariam T, Dobner B , et al. Skin diseases associated with the depletion of stratum corneum lipids and stratum corneum lipid substitution therapy. Skin Pharmacol Physiol 2015; 28(1):42-55. doi: 10.1159/000360009.
28.	Elsholz F, Harteneck C, Muller W , et al. Calcium—a central regulator of keratinocyte differentiation in health and disease. Eur J Dermatol 2014; 24(6):650-61. doi: 10.1684/ejd.2014.2452. doi: 10.1684/ejd.2014.2452
29.	Gschwandtner M, Mildner M, Mlitz V , et al. Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model. Allergy 2013; 68(1):37-47. doi: 10.1111/all.12051. doi: 10.1111/all.12051
30.	Gutowska-Owsiak D, Ogg GS . Cytokine regulation of the epidermal barrier. Clin Exp Allergy 2013; 43(6):586-98. doi: 10.1111/cea.12023. doi: 10.1111/cea.12023
31.	Iizuka H, Takahashi H, Honma M , et al. Unique keratinization process in psoriasis: late differentiation markers are abolished because of the premature cell death. J Dermatol 2004; 31(4):271-6.
32.	Dugu L, Nakahara T, Wu Z , et al. Neuronatin is related to keratinocyte differentiation by up-regulating involucrin. J Dermatol Sci 2014; 73(3):225-31. doi: 10.1016/j.jdermsci.2013.10.008. doi: 10.1016/j.jdermsci.2013.10.008
33.	Kage M, Tokudome Y, Matsunaga Y , et al. Effect of hyaluronan tetrasaccharides on epidermal differentiation in normal human epidermal keratinocytes. Int J Cosmet Sci 2014; 36(1):109-15. doi: 10.1111/ics.12105.
34.	Donetti E, Cornaghi L, Arnaboldi F , et al. Interleukin 22 early affects keratinocyte differentiation, but not proliferation, in a three-dimensional model of normal human skin. Exp Cell Res 2016; 345(2):247-54. doi: 10.1016/j.yexcr.2016.05.004.
35.	Gelfant S . The cell cycle in psoriasis: a reappraisal. Br J Dermatol 1976; 95(6):577-90.
36.	Javier AF, Bata-Csorgo Z, Ellis CN , et al. Rapamycin (sirolimus) inhibits proliferating cell nuclear antigen expression and blocks cell cycle in the G1 phase in human keratinocyte stem cells. J Clin Invest 1997; 99(9):2094-9. doi: 10.1172/JCI119382.
37.	Zhang Y, Tu C, Zhang D , et al. Wnt/beta-catenin and Wnt5a/Ca pathways regulate proliferation and apoptosis of keratinocytes in psoriasis lesions. Cell Physiol Biochem 2015; 36(5):1890-902. doi: 10.1159/000430158.
38.	Wrone-Smith T, Mitra RS, Thompson CB , et al. Keratinocytes derived from psoriatic plaques are resistant to apoptosis compared with normal skin. Am J Pathol 1997; 151(5):1321-9.

[1]	He Qiong, Wang Hui-hui, Cheng Tao, Yuan Wei-ping, Ma Yu-po, Jiang Yong-ping, Ren Zhi-hua. Genetic Correction and Hepatic Differentiation of Hemophilia B-specific Human Induced Pluripotent Stem Cells [J]. Chinese Medical Sciences Journal, 2017, 32(3): 135-144.
[2]	Du Tingting, Liu Na, Gu Bin, Li Ying, Yuan Yifang, Zhang Wei, Zhang Tong. Effects of Aging on the Proliferation and Differentiation Capacity of Human Periodontal Ligament Stem Cells^△ [J]. Chinese Medical Sciences Journal, 2017, 32(2): 83-91.
[3]	Liang Wang, Zheng-yao Li, Yi-peng Wang*, Zhi-hong Wu, Bin Yu. Dynamic Expression Profiles of Marker Genes in Osteogenic Differentiation of Human Bone Marrow-derived Mesenchymal Stem Cells [J]. Chinese Medical Sciences Journal, 2015, 30(2): 108-113.
[4]	Yi Liu, Jian-ping Gong, Wen-fang Li. Therapeutic Effect and Safety of Ustekinumab for Plaque Psoriasis: A Meta-analysis [J]. Chinese Medical Sciences Journal, 2014, 29(3): 131-138.
[5]	Rui-feng Yang, Guo-wei Zhao, Shu-ting Liang, Hou-zao Chen, and De-pei Liu. Lysine-specific Demethylase 1 Represses THP-1 Monocyte-to-macrophage Differentiation^025B3; [J]. Chinese Medical Sciences Journal, 2013, 28(2): 82-87.
[6]	Li Zhang, Li Yan, Ye Zhang, Ning-hua Wu and Yu-fei Shen. Role of Acetylated p53 in Regulating the Expression of map2 in Retinoic Acid-induced P19 Cells [J]. Chinese Medical Sciences Journal, 2010, 25(2): 71-75.

Early edition

Current issue

Archive

Specialties & Topics

Author center

Reviewer center

IL-36β Promotes Inflammatory Activity and Inhibits Differentiation of Keratinocytes In Vitro

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 2

References 38.

Related Articles 6

Metrics

Recommended 10