Hypoxia-Exosome Mesenchymal Stem Cells Therapy Reduces Interleukin-6 Levels and CD86 Expression

Adelia Bayu Isfandiari, Agung Putra, Eko Setiawan

Abstract


Background: UVB exposure activates type 1 macrophages (CD86) and increases IL-6, both contributing to collagen loss. exosome hypoxia mesenchymal stem cells (EH-MSC) has anti-inflammatory properties, suggesting its potential role in modulating CD86 activation and IL-6 secretion. This study examines the effects of EH-MSC injections on CD86 and IL-6 levels in UVB-exposed skin with collagen loss.

Materials and methods: Experimental research post-test only control group design was conducted with 30 male Wistar rats (Rattus norvegicus, strain: Wistar Han) divided into five groups. G1: healthy rats, G2: UVB-exposed with a subcutaneous injection of 0.9% NaCl, G3: UVB-exposed with Hyaluronic Acid, and G4 & G5: UVB-exposed with EH-MSC injections of 200 µL and 300 µL, respectively. IL-6 and CD86 levels were analysed using ELISA and qRT-PCR at 14 days post-treatment continue with statistical analysis.

Results: IL-6 analysis showed that levels in G4 (107.70±47.86 pg/mL) and G5 (58.68±25.37 pg/mL) were notably lower than in G2 and G3 (p<0.05). Compared to G1 (32.28±14.65 pg/mL), G4 exhibited a statistically distinct increase (p<0.05), whereas G5 showed no significant difference (p>0.05). Meanwhile, CD86 data analysis showed that G4 (0.53±0.14 pg/mL) were lower than in G1 (1.03±0.01 pg/mL) and G2 (1.47±0.43 pg/mL), but not significantly different from G3 (0.87±0.1 pg/mL) and G5 (0.36±0.08 pg/mL). Similarly, CD86 expression in G5 decreased relative to G1 and G2 (p<0.05) but remained similar to G3 and G4.

Conclusion: EH-MSC injections (200 µL and 300 µL) significantly reduced IL-6 and CD86 levels in collagen loss rats, supporting its potential as a therapeutic approach for UVB-induced skin damage.

Keywords: collagen loss, CD86, EH-MSC, IL-6, UVB


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References


Shah K, Minkis K, Swary JH, Alam M. Photoaging. In: Draelos ZD, editor. Cosmetic Dermatology. Hoboken, NJ: Wiley; 2022. p.16-25, CrossRef.

Tang CH, Chen CF, Chen WM, Fong YC. IL-6 Increases MMP-13 expression and motility in human chondrosarcoma cells. J Biol Chem. 2011; 286(13): 11056-66, CrossRef.

Hiromi N, Nakano H, Matsuzaki Y, Sawamura D, Hanada K. Immunohistochemical analysis of in vivo UVB-induced secretion of IL-1α and IL-6 in keratinocytes. Mol Med Rep. 2011; 4(4): 611-4, CrossRef.

Park G, Qian W, Zhang MJ, Chen YH, Ma LW, Zeng N, et al. Platelet-rich plasma regulating the repair of ultraviolet B-induced acute tissue inflammation: Adjusting macrophage polarization through the activin receptor-follistatin system. Bioengineered. 2021; 12(1): 3125-36, CrossRef.

Sharma MR, Mitrani R, Werth VP. Effect of TNFα blockade on UVB-induced inflammatory cell migration and collagen loss in mice. J Photochem Photobiol B. 2020; 213: 112072, CrossRef.

Cai G, Cai G, Zhou H, Zhuang Z, Liu K, Pei S, et al. Mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction. Stem Cell Res Ther. 2021; 12(1): 2. doi: 10.1186/s13287-020-02030-w. Retraction in: Stem Cell Res Ther. 2023; 14(1): 9, CrossRef.

Bu T, Li Z, Hou Y, Sun W, Zhang R, Zhao L, et al. Exosome-mediated delivery of inflammation-responsive Il-10 mRNA for controlled atherosclerosis treatment. Theranostics. 2021; 11(20): 9988-10000, CrossRef.

Duan J, Li Y, Gao J, Cao R, Shang E, Zhang W. ROS-mediated photoaging pathways of nano- and micro-plastic particles under UV irradiation. Water Res. 2022; 216: 118320, CrossRef.

Kartika R, Wibowo H. Impaired function of regulatory T cells in type 2 diabetes mellitus. Mol Cell Biomed Sci. 2020; 4(1): 1-9, CrossRef.

Aryana IGPS, Hapsari AAAR, Kuswardhani RAT. Myokine regulation as marker of sarcopenia in elderly. Mol Cell Biomed Sci. 2018; 2(2): 38-47, CrossRef.

Kleine‐Börger L, Meyer R, Kalies A, Kerscher M. Approach to differentiate between hyaluronic acid skin quality boosters and fillers based on their physicochemical properties. J Cosmet Dermatol. 2022; 21(1): 149-57, CrossRef.

Espinoza L, Vinshtok Y, McCreesh J, Tyson J, McSorley M. Kinetic energy-assisted delivery of hyaluronic acid for skin remodeling in middle and lower face. J Cosmet Dermatol. 2020; 19(9): 2277-81, CrossRef.

Grégoire S, Man PD, Maudet A, Le Tertre M, Hicham N, Changey F, et al. Hyaluronic acid skin penetration evaluated by tape stripping using ELISA kit assay. J Pharm Biomed Anal. 2023; 224: 115205, CrossRef.

Chircov C, Grumezescu AM, Bejenaru LE. Hyaluronic acid-based scaffolds for tissue engineering. Rom J Morphol Embryol. 2018; 59(1): 71-6, article.

Zhao C, Chen JY, Peng WM, Yuan B, Bi Q, Xu YJ. Exosomes from adipose derived stem cells promote chondrogenesis and suppress inflammation by upregulating miR 145 and miR 221. Mol Med Rep. 2020; 21(4): 1881-9, CrossRef.

Eshghi F, Tahmasebi S, Alimohammadi M, Soudi S, Khaligh SG, Khosrojerdi A, et al. Study of immunomodulatory effects of mesenchymal stem cell-derived exosomes in a mouse model of LPS induced systemic inflammation. Life Sci. 2022; 310: 120938, CrossRef.

Kheirkhah AH, Shahcheraghi SH, lotfi M, lotfi M, Raeisi S, Mirani Z. Mesenchymal stem cell derived-exosomes as effective factors in reducing cytokine storm symptoms of COVID-19. Protein Pept Lett. 2021; 28(8): 945-52, CrossRef.

Yang H, Chen J. Bone marrow mesenchymal stem cell-derived exosomes carrying long noncoding RNA ZFAS1 alleviate oxidative stress and inflammation in ischemic stroke by inhibiting microRNA-15a-5p. Metab Brain Dis. 2022; 37(7): 2545-57, CrossRef.

Singla D, Johnson T, Tavakoli Dargani Z. Exosome treatment enhances anti-inflammatory M2 macrophages and reduces inflammation-induced pyroptosis in doxorubicin-induced cardiomyopathy. Cells. 2019; 8(10): 1224, CrossRef.

Kim M, Shin D Il, Choi BH, Min BH. Exosomes from IL-1β-primed mesenchymal stem cells inhibited IL-1β- and TNF-α-mediated inflammatory responses in osteoarthritic SW982 cells. Tissue Eng Regen Med. 2021; 18(4): 525-36, CrossRef.

Chouw A, Triana R, Dewi NM, Darmayanti S, Rahman MN, Susanto A, et al. Ischemic stroke: New neuron recovery approach with mesenchymal and neural stem cells. Mol Cell Biomed Sci. 2018; 2(2): 48-54, CrossRef.

Kim HN, Gil CH, Kim YR, Shin HK, Choi BT. Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice. Sci Rep. 2016; 6(1): 31169, CrossRef.

Sofyanti Putri R, Putra A, Chodidjah D, Masyitah Darlan D, Trisnadi S, Thomas S, et al. Clitorea ternatea flower extract induces platelet-derived growth factor (PDGF) and GPx gene overexpression in ultraviolet (UV) B irradiationinduced collagen loss. Med Glas. 2022; 20(1): 15-21, CrossRef.

Chandel NS, Trzyna WC, McClintock DS, Schumacker PT. Role of oxidants in NF-κB activation and TNF-α gene transcription induced by hypoxia and endotoxin. J Immunol. 2000; 165(2): 1013-21, CrossRef.

Yang YN, Wang F, Zhou W, Wu ZQ, Xing YQ. TNF-α stimulates MMP-2 and MMP-9 activities in human corneal epithelial cells via the activation of FAK/ERK signaling. Ophthalmic Res. 2012; 48(4): 165-70, CrossRef.

Mirastschijski U, Lupše B, Maedler K, Sarma B, Radtke A, Belge G, et al. Matrix metalloproteinase-3 is key effector of TNF-α-induced collagen degradation in skin. Int J Mol Sci. 2019; 20(20): 5234, CrossRef.

Norouzi-Barough L, Shirian S, Gorji A, Sadeghi M. Therapeutic potential of mesenchymal stem cell-derived exosomes as a cell-free therapy approach for the treatment of skin, bone, and cartilage defects. Connect Tissue Res. 2022; 63(2): 83-96, CrossRef.

Ha DH, Kim H keun, Lee J, Kwon HH, Park GH, Yang SH, et al. Mesenchymal stem/stromal cell-derived exosomes for immunomodulatory therapeutics and skin regeneration. Cells. 2020; 9(5): 1157, CrossRef.

Zhang B, Wang M, Gong A, Zhang X, Wu X, Zhu Y, et al. HucMSC-exosome mediated-wnt4 signaling is required for cutaneous wound healing. Stem Cells. 2015; 33(7): 2158-68, CrossRef.

Wang X, Liu Y, He J, Wang J, Chen X, Yang R. Regulation of signaling pathways in hair follicle stem cells. Burns Trauma. 2022; 10: tkac022, CrossRef.

Nguyen Hong S, Dinh Huu N, Nguyen Duy N, Than Trong T, Nguyen Bac H, Nguyen Van T, et al. Serial excision for the treatment of giant congenital melanocytic nevus: The Vietnamese way. Maced J Med Sci. 2019; 7(2): 231-3, CrossRef.

Nejati S, Mongeau L. Injectable, pore-forming, self-healing, and adhesive hyaluronan hydrogels for soft tissue engineering applications. Sci Rep. 2023; 13(1): 14303, CrossRef.

Bashir MM, Sharma MR, Werth VP. UVB and proinflammatory cytokines synergistically activate TNF-alpha production in keratinocytes through enhanced gene transcription. J Invest Dermatol. 2009; 129(4): 994-1001, CrossRef.




DOI: https://doi.org/10.21705/mcbs.v9i3.660

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