Tín hiệu SIGIRR-caspase-8 điều hòa sự apoptosis của tế bào nội mô trong bệnh Kawasaki

Italian Journal of Pediatrics - Tập 49 - Trang 1-12 - 2023
Zhengwang Wen1,2,3, Yuhan Xia1,2,3, Yingying Zhang1,2,3, Yuxi He1,2,3, Chao Niu2,3, Rongzhou Wu1, Chunxiang Zhang1, Chang Jia1,2,3, Xing Rong1, Maoping Chu1,2,3
1Children’s Heart Center, Institute of Cardiovascular Development and Translational Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
2Pediatric Research Institute, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
3Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, China

Tóm tắt

Bệnh Kawasaki (KD) là một loại viêm mạch với nguyên nhân chưa được xác định. Vì hiện tại, chẩn đoán và chiến lược điều trị bệnh KD chủ yếu phụ thuộc vào kinh nghiệm lâm sàng, cần thiết phải có thêm nghiên cứu để khám phá các cơ chế bệnh lý của nó. Phương pháp enzyme linked immunosorbent assay (ELISA) được sử dụng để đo nồng độ SIGIRR, TLR4 và caspase-8 trong huyết thanh. Phương pháp Western blotting được áp dụng để xác định nồng độ protein, còn phân tích dòng tế bào được thực hiện để khảo sát sự apoptosis của tế bào. Nhuộm Hematoxylin eosin (HE) và nhuộm TUNEL lần lượt được sử dụng để quan sát tình trạng viêm động mạch vành và phân mảnh DNA. Trong nghiên cứu này, chúng tôi phát hiện rằng nồng độ SIGIRR giảm trong huyết thanh KD và tế bào nội mô được điều trị bằng huyết thanh KD. Tuy nhiên, nồng độ caspase-8 tăng lên trong huyết thanh của bệnh nhân KD so với nhóm đối chứng khỏe mạnh (HC). Do đó, chúng tôi giả thuyết rằng tín hiệu SIGIRR-caspase-8 có thể đóng một vai trò quan trọng trong sinh lý bệnh của KD. Các thí nghiệm in vitro cho thấy sự apoptosis của tế bào nội mô trong bối cảnh KD có liên quan đến việc kích hoạt caspase-8, và biểu hiện quá mức SIGIRR làm giảm thiểu sự apoptosis của tế bào nội mô thông qua việc ức chế kích hoạt caspase-8. Những phát hiện này cũng được tái hiện trong mô hình chuột mắc KD được kích thích bởi chiết xuất màng tế bào Candida albicans (CAWS). Dữ liệu của chúng tôi cho thấy rằng sự apoptosis của tế bào nội mô do tín hiệu SIGIRR-caspase-8 điều hòa đóng một vai trò quan trọng trong tổn thương nội mô động mạch vành, cung cấp các mục tiêu tiềm năng để điều trị KD.

Từ khóa

#bệnh Kawasaki #SIGIRR #caspase-8 #tế bào nội mô #apoptosis

Tài liệu tham khảo

Rife E, Gedalia A. Kawasaki disease: an update. Curr Rheumatol Rep. 2020;22:1–10. https://doi.org/10.1007/s11926-020-00941-4. Newburger JW, Takahashi M, Burns JC. Kawasaki disease. J Am Coll Cardiol. 2016;67:1738–49. https://doi.org/10.1016/j.jacc.2015.12.073. He M, Chen Z, Martin M, Zhang J, Sangwung P, Woo B, Tremoulet AH, Shimizu C, Jain MK, Burns JC, Shyy JY. MiR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition: Therapeutic Implications in Kawasaki Disease. Circ Res. 2017;120:354–65. https://doi.org/10.1161/CIRCRESAHA.116.310233. Chu M, Wu R, Qin S, Hua W, Shan Z, Rong X, Zeng J, Hong L, Sun Y, Liu Y, Li W, Wang S, Zhang C. Bone Marrow-Derived MicroRNA-223 Works as an Endocrine Genetic Signal in Vascular Endothelial Cells and Participates in Vascular Injury From Kawasaki Disease. J Am Heart Assoc. 2017;6:1–14. https://doi.org/10.1161/JAHA.116.004878. Jia C, Zhuge Y, Zhang S, Ni C, Wang L, Wu R, Niu C, Wen Z, Rong X, Qiu H, Chu M. IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway. Cell Death Dis. 2021;12:575. https://doi.org/10.1038/s41419-021-03852-z. Jia C, Zhang J, Chen H, Zhuge Y, Chen H, Qian F, Zhou K, Niu C, Wang F, Qiu H, Wang Z, Xiao J, Rong X, Chu M. Endothelial cell pyroptosis plays an important role in Kawasaki disease via HMGB1/RAGE/cathespin B signaling pathway and NLRP3 inflammasome activation. Cell Death Dis. 2019;10:778. https://doi.org/10.1038/s41419-019-2021-3. Li D, Zhang X, Chen B. SIGIRR participates in negative regulation of LPS response and tolerance in human bladder epithelial cells. BMC Immunol. 2015;16:73. https://doi.org/10.1186/s12865-015-0137-5. Joosten LA, Abdollahi-Roodsaz S, Dinarello CA, O’Neill L, Netea MG. Toll-like receptors and chronic inflammation in rheumatic diseases: new developments, Nature reviews. Rheumatology. 2016;12:344–57. https://doi.org/10.1038/nrrheum.2016.61. Wang GB, Li CR, Zu Y, Yuan XW. The role of activation of toll-like receptors in immunological pathogenesis of Kawasaki disease. Chin J Pediatr. 2006;44:333–6 https://www.ncbi.nlm.nih.gov/pubmed/16780707. Tang B, Lo HH, Lei C, U KI, Hsiao WW, Guo X, Bai J, Wong VK, Law BY. Adjuvant herbal therapy for targeting susceptibility genes to Kawasaki disease: An overview of epidemiology, pathogenesis, diagnosis and pharmacological treatment of Kawasaki disease. Phytomedicine. 2020;70:153208. https://doi.org/10.1016/j.phymed.2020.153208. Liu J, Chen Y, Liu D, Liu W, Hu S, Zhou N, Xie Y. Ectopic expression of SIGIRR in the colon ameliorates colitis in mice by downregulating TLR4/NF-κB overactivation. Immunol Lett. 2017;183:52–61. https://doi.org/10.1016/j.imlet.2017.01.015. Ohno N. Murine model of Kawasaki disease induced by mannoprotein-beta-glucan complex, CAWS, obtained from Candida albicans. Jpn J Infect Dis. 2004;57:S9–10 https://www.ncbi.nlm.nih.gov/pubmed/15507772. Lun Y, Borjini N, Miura NN, Ohno N, Singer NG, Lin F. CDCP1 on Dendritic Cells Contributes to the Development of a Model of Kawasaki Disease. J Immunol. 2021;12:2819–27. https://doi.org/10.4049/jimmunol.2001406. Stock AT, Hansen JA, Sleeman MA, McKenzie BS, Wicks IP. GM-CSF primes cardiac inflammation in a mouse model of Kawasaki disease GM-CSF triggers cardiac inflammation. J Exp Med. 2016;213:1983–98. https://doi.org/10.1084/jem.20151853. Loo DT. In situ detection of apoptosis by the TUNEL assay: an overview of techniques. Methods Mol Biol (Clifton, NJ). 2011;682:3–13. https://doi.org/10.1007/978-1-60327-409-8_1. Bruggisser J, Tarek B, Wyder M, Müller P, von Ballmoos C, Witz G, Enzmann G, Deutsch U, Engelhardt B, Posthaus H. CD31(PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin. Cell Host Microbe. 2020;28:69–78.e6. https://doi.org/10.1016/j.chom.2020.05.003. Shi H, Sun L, Wang Y, Liu A, Zhan X, Li X, Tang M, Anderton P, Hildebrand S, Quan J, Ludwig S, Moresco EMY, Beutler B. N4BP1 negatively regulates NF-κB by binding and inhibiting NEMO oligomerizatio. Nat Commun. 2021;12:1379. https://doi.org/10.1038/s41467-021-21711-5. Sun Y, Chen H, Lin Y. Rehabilitation training inhibits neuronal apoptosis by down-regulation of TLR4/MyD88 signaling pathway in mice with cerebral ischemic stroke. Am J Transl Res. 2021;13:2213–23. https://www.ncbi.nlm.nih.gov/pubmed/34017384. Shalini S, Dorstyn L, Dawar S, Kumar S. Old, new and emerging functions of caspases. Cell Death Differ. 2015;22:526–39. https://doi.org/10.1038/cdd.2014.216. Jiang C, Fang X, Jiang Y, Shen F, Hu Z, Li X, Huang X. TNF-α induces vascular endothelial cells apoptosis through overexpressing pregnancy induced noncoding RNA in Kawasaki disease model. Int J Biochem Cell Biol. 2016;72:118–24. https://doi.org/10.1016/j.biocel.2016.01.011. Wu R, Shen D, Sohun H, Ge D, Chen X, Wang X, Chen R, Wu Y, Zeng J, Rong X, Su X, Chu M. miR-186, a serum microRNA, induces endothelial cell apoptosis by targeting SMAD6 in Kawasaki disease. Int J Mol Med. 2018;41:1899–908. https://doi.org/10.3892/ijmm.2018.3397. Qi Z, Yan D, Cao L, Xu Y, Chang M. Zebrafish BID Exerts an Antibacterial Role by Negatively Regulating p53, but in a Caspase-8-Independent Manner. Front Immunol. 2021;12:707426. https://doi.org/10.3389/fimmu.2021.707426. Xu Z, Chen X, Fu S, Bao J, Dang Y, Huang M, Chen L, Wang Y. Dehydrocorydaline inhibits breast cancer cells proliferation by inducing apoptosis in MCF-7 cells. Am J Chin Med. 2012;40:177–85. https://doi.org/10.1142/S0192415X12500140. Tullus K, Marks SD. Vasculitis in children and adolescents. Pediatr Drugs. 2009;11:375–80. https://doi.org/10.2165/11316120-000000000-00000. Zhao QM, Huang M, Huang MR, Chen S, Liu F, Huang GY. Shanghai Kawasaki Disease Research Group, Characteristics and trends in diagnosis of Kawasaki disease outside the usual age range. Clin Rheumatol. 2021;40:1515–23. https://doi.org/10.1007/s10067-020-05361-4. Rocha DM, Caldas AP, Oliveira LL, Bressan J, Hermsdorff HH. Saturated fatty acids trigger TLR4-mediated inflammatory response. Atherosclerosis. 2016;244:211–5. https://doi.org/10.1016/j.atherosclerosis.2015.11.015. Wu Y, Wang Y, Gong S, Tang J, Zhang J, Li F, Yu B, Zhang Y, Kou J. Ruscogenin alleviates LPS-induced pulmonary endothelial cell apoptosis by suppressing TLR4 signaling. Biomed Pharmacother. 2020;125:109868. https://doi.org/10.1016/j.biopha.2020.109868. Chi W, Li F, Chen H, Wang Y, Zhu Y, Yang X, Zhu J, Wu F, Ouyang H, Ge J, Weinreb RN, Zhang K, Zhuo Y. Caspase-8 promotes NLRP1/NLRP3 inflammasome activation and IL-1β production in acute glaucoma. P Natl Acad Sci USA. 2014;111:11181–6. https://doi.org/10.1073/pnas.1402819111. Li XM, Su JR, Yan SP, Cheng ZL, Yang TT, Zhu Q. A novel inflammatory regulator TIPE2 inhibits TLR4-mediated development of colon cancer via caspase-8. Cancer Biomark. 2014;14:233–40. https://doi.org/10.3233/CBM-140402. Li L, Wei J, Li S, Jacko AM, Weathington NM, Mallampalli RK, Zhao J, Zhao Y. The deubiquitinase USP13 stabilizes the anti-inflammatory receptor IL-1R8/Sigirr to suppress lung inflammation. EBioMedicine. 2019;45:553–62. https://doi.org/10.1016/j.ebiom.2019.06.011. Gong J, Wei T, Stark RW, Jamitzky F, Heckl WM, Anders HJ, Lech M, Rossle SC. Inhibition of Toll-like receptors TLR4 and 7 signaling pathways by SIGIRR: a computational approach. J Struct Biol. 2010;169:323–30. https://doi.org/10.1016/j.jsb.2009.12.007. Qin J, Qian Y, Yao J, Grace C, Li X. SIGIRR inhibits interleukin-1 receptor-and toll-like receptor 4-mediated signaling through different mechanisms. J Biol Chem. 2005;280:25233–41. https://doi.org/10.1074/jbc.M501363200. Yamaguchi R, Sakamoto A, Yamamoto T, Narahara S, Sugiuchi H, Yamaguchi Y. Differential regulation of IL-23 production in M1 macrophages by TIR8/SIGIRR through TLR4- or TLR7/8-mediated signaling. Cytokine. 2017;99:310–5. https://doi.org/10.1016/j.cyto.2017.08.014. Riva F, Bonavita E, Barbati E, Muzio M, Mantovani A, Garlanda C. TIR8/SIGIRR is an interleukin-1 receptor/toll like receptor family member with regulatory functions in inflammation and immunity. Front Immunol. 2012;3:322. https://doi.org/10.3389/fimmu.2012.00322.
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Italian Journal of Pediatrics

Tập 49

1-12

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