Effect of astragaloside IV on the immunoregulatory function of adipose-derived mesenchymal stem cells from patients with psoriasis vulgaris

doi:10.19852/j.cnki.jtcm.20220516.002

Abstract

Abstract:

OBJECTIVE: To compare the phenotype and adipogenic and osteogenic differentiation capacities of adipose-derived mesenchymal stem cells (AMSCs) isolated from patients with psoriasis vulgaris and healthy donors, and to explore the effects of astragaloside IV, a Traditional Chinese Medicine, on the immunoregulatory function of AMSCs. METHODS: AMSCs were isolated from human adipose tissue and cultured for three generations in vitro. Cell phenotype and cell cycle analysis were performed by flow cytometry. Adipogenic and osteogenic differentiation of AMSCs was examined by lipid (oil red O) and alkaline phosphatase staining, respectively. Expression of inflammatory mediators was examined by real-time quantitative polymerase chain reaction analysis, and proliferation was quantified using the cell counting kit-8 assay. RESULTS: Expression of CD29, CD44, and CD73 was higher in AMSCs from healthy donors than psoriasis patients, while the reverse was true for expression of CD45, CD31, and HLA-DR. AMSCs from psoriasis patients had a greater ability to undergo adipogenic differentiation than cells from healthy donors, whereas there was no significant difference in osteogenic differentiation between AMSCs from the two sources. Compared with AMSCs from healthy donors, psoriasis patient-derived AMSCs expressed lower levels of the anti-inflammatory cytokines interleukin-10 and trans-forming growth factor-β (TGF-β) and the immune checkpoint ligand programmed cell death 1 ligand 1 (PD-L1) (P < 0.05) and higher levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Incubation of AMSCs from psoriasis patients with astragaloside IV had no significant effect on pro-liferation but increased the expression of TGF-β and PD-L1 and decreased the expression of IFN-γ and TNF-α. CONCLUSION: AMSCs from patients with psoriasis vulgaris display abnormal proliferation and adipogenesis and an enhanced pro-inflammatory phenotype. These defects were normalized by treatment with astragaloside IV, suggesting that this Traditional Chinese Medicine may be useful for restoring the immunoregulatory function of AMSCs and immune homeostasis in patients with psoriasis vulgaris.

Key words: psoriasis, mesenchymal stem cells, cell proliferation, astragaloside IV, adipogenesis, osteogenesis, immune regulation

YIN Xiuping, ZHANG Xiaotong, ZHU Rongjia, SONG Ping. Effect of astragaloside IV on the immunoregulatory function of adipose-derived mesenchymal stem cells from patients with psoriasis vulgaris[J]. Journal of Traditional Chinese Medicine, 2022, 42(4): 513-519.

Figures/Tables 4

Figure 1 Cell cycle analysis of AMSCs from psoriasis patients and healthy donors A: flow cytometric analysis of propidium iodide-stained third-generation AMSCs (adipose-derived mesenchymal stem cells) derived from healthy donors; B: flow cytometric analysis of propidium iodide-stained third-generation AMSCs derived from psoriasis patients; C: quantification of AMSCs of healthy donors and psoriasis patients in the indicated cell cycle stages. AMSCs: adipose-derived mesenchymal stem cells. Compared with the healthy donors AMSCs, aP < 0.05.

Figure 2 Induction of adipogenic and osteogenic differentiation in cultured AMSCs A, C: third generation AMSCs from psoriasis patients; B, D: third generation AMSCs from healthy donors. A, B: induction of adipogenic differentiation of AMSCs by Oil Red O staining on day 13 (× 20); C, D: induction of osteogenic differentiation of AMSCs by alkaline phosphatase staining on day 6 (× 20). AMSCs: adipose-derived mesenchymal stem cells.

Table 1 RT-qPCR analysis of the indicated cytokines or PD-L1 in AMSCs from healthy donors compared with those from psoriasis patients ($\bar{x}±s$)

Group	n	IL-10	TGF-β	PD-L1	IFN-γ	TNF-α
Psoriasis AMSCs	3	0.33±0.08	0.98±0.14	0.23±0.04^a	2.34±1.63	1.31±0.24
Healthy AMSCs	3	1.00±0.42	1.00±0.19	1.00±0.18	1.00±0.57	1.00±0.46

Table 2 Effect of astragaloside IV on the expression of cytokines and PD-L1 by AMSCs from psoriasis patients ($\bar{x}±s$)

Group	n	IL-10	TGF-β	PD-L1	IFN-γ	TNF-α
Control	3	1.00±0.25	1.00±0.14	1.00±0.16	1.00±0.33	1.00±0.17
As1	3	0.97±0.24	1.17±0.13	1.09±0.21	0.01±0.34^b	0.77±0.27
As2	3	1.10±0.18	1.57±0.20^a	1.82±0.27^a	0.42±0.36^a	1.02±0.29
As3	3	1.08±0.34	1.36±0.35	1.82±0.51^a	0.41±0.17^a	0.95±0.22

References 19

1	Mahler, Jackson C, Ijacu H. The burden of psoriasis and barriers to satisfactory care: results from a Canadian patient survery. J Cutan Med Surg 2009; 13: 283-93. DOI URL
2	Akiyama K, Chen C, Wang DD, et al. Mesenchymalstem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem cell 2012; 10: 544-55. DOI URL
3	Li Q, Ma Y, Li L, et al. Flagellin influences the expression of a variety of important cytokines and chemokines without affecting the immune status of umbilical cord mesenchymal stem cells. Mol Med Rep 2015; 12: 6955-61. DOI URL
4	Cao K, Zhang T. Progress in immunoregulatory plasticity of mesenchymal stem cells. Medical review 2018; 24 : 34-9.
5	Zhou DM, Wang P, Chen WW, et al. An analysis of the theoretical evolution from treating psoriasis from blood to Qi, blood and body fluid. Beijing Zhong Yi Yao 2019; 38: 755-9.
6	Zhang K, Liu R, Yin G, et al. Differential cytokine secretion of cultured bone marrow stromal cells from patiens with psoriasis and healthy volunteers. Eur J Dermatol 2010; 20, 49-53. DOI URL
7	Peng SN, Tao YX, Hong T, et al. Astragaloside Ⅳ regulating differentiation of splenic lymphocyte of IgA nephropathy rats via mTORC 1 pathway. Zhong Guo Mian Yi Xue Za Zhi 2021; 37: 421-5.
8	Zhou X, Liu Rf, Zhang K, et al. Detection of interleukin and vascular endothelial growth factor secreted by psoriatic bone marrow mesenchymal stem cells. Lin Chuang Pi Fu Za Zhi 2014; 5: 22-8.
9	Hou R, Liu R, Niu X, et al. Biological characteristics and gene expression pattern of bone marrow mesenchymal stem cells in patients with psoriasis. Exp Dermatol 2014; 23: 521-3. DOI URL
10	Munir H, Ward LSC, Sheriff L, et al. Adipogenic differentiation of MSC alters their immunomodulatory properties in a tissue-specific manner. Stem Cells 2017; 35: 1636-46. DOI URL
11	Jia YR, Jia XL, Hou RX, et al. Gene expression and biological characteristics of bone marrow mesenchymal stem cells in patients with psoriasis. Shanxi Yi Yao Za Zhi 2016; 45: 20-3.
12	Kode JA, Mukherjee S, Joglekar MV, et al. Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration. Cytotherapy 2009; 11: 377-91. DOI URL
13	English K. Mechanisms of mesenchymal stromal celli-mmunomodulation. Immunol Cell Biol 2013; 91: 19-26. DOI PMID
14	Qu X, Liu X, Cheng K, et al. Mesenchymal stem cells inhibit Th17 cell differentiation by IL-10 secretion. Exp Hematol 2012; 40: 761-70. DOI URL
15	Huang QL, Wei XF. Plasticity of immune regulation of mesenchymal stem cells. Zhong Guo Ke Xue: Sheng Ming Ke Xue 2016; 46: 79-808.
16	Waterman RS, Tomchuck SL, Henkle SL, et al. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLoS One 2010; 5: e10088.
17	Zhong QC. Discussing the pathogenesis and treatment of systemic lupus erythematosus from the connection between Traditional Chinese Medicine and modern immunology. Xin Zhong Yi 2004; 36: 3-6.
18	Song P, Wang XX, Yang MY, et al. Observation of 120 cases of plaque psoriasis treated by opening Xuanfu and dredging collaterals and detoxifying methods. Zhong Yi Za Zhi 2013; 54: 1476-1479.
19	Yin XP. Zhou RJ, Zhuang C, et al. Isolating culture of adipose mesenchymal stem cells in psoriasis vulgaris patients and differentiation into immune regulation function. Ji Chu Yi Xue Yu Lin Chuang 2017; 37: 975-80.

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