IL-33/ST2信号通路与骨代谢的研究进展
|
摘要
白细胞介素-33(interleukin-33,IL-33)是白细胞介素-1(interleukin-1,IL-1)细胞因子超家族的一个新成员,它可以激活肥大细胞、淋巴细胞、巨噬细胞,产生Th2细胞因子,并且在炎症、感染、自身免疫性疾病中发挥其重要作用。IL-33的经典信号途径是通过ST2和IL-1受体辅助蛋白(interleukin-1 receptor accessory protein,IL-1 RAcP)组成的异三聚体,将信号转导至细胞内。IL-33/ST2信号通路通过激活T、B淋巴细胞等方面影响骨代谢。本文就IL-33/ST2信号通路在骨代谢中的作用研究作一综述,复习文献结果表明,IL-33在骨代谢方面的作用仍存在争议,一些学者研究认为IL-33可抑制破骨细胞的生成,并且在生理性骨重建中起作用;但也有学者认为IL-33可促进破骨细胞的形成及分化,从而导致骨吸收。IL-33及其信号通路参与牙周炎及根尖周炎牙槽骨骨代谢,具体机制尚不清楚,还需进一步研究。
Interleukin-33(IL-33) is a new member of the interleukin-1(IL-1) cytokine superfamily. It can activate mast cells, lymphocytes and macrophages to produce Th2 cytokines and plays a very important role in inflammation, infection, and autoimmune disease. The classical signal pathway of IL-33 includes the isotrimer of ST2 and interleukin-1 receptor accessory protein(IL-1 RAcP), which transduces signals into cells. The IL-33/ST2 signaling pathway affects bone metabolism by activating T and B lymphocytes. This article reviews the role of the IL-33/ST2 signaling pathway in bone metabolism. The results of a literature review showed that at present, scholars at home and abroad still dispute the role of IL-33 in bone metabolism. Some scholars believe that IL-33 can inhibit osteoclast formation, and IL-33 has been recently implicated in physiological bone remodeling. However, other scholars believe that IL-33 can promote osteoclast formation and differentiation, which leads to bone absorption. IL-33 and its signaling pathway are involved in bone metabolism of alveolar bone in periodontitis and periapical periodontitis. The specific mechanism remains unclear, and further studies are warranted.
Interleukin-33(IL-33) is a new member of the interleukin-1(IL-1) cytokine superfamily. It can activate mast cells, lymphocytes and macrophages to produce Th2 cytokines and plays a very important role in inflammation, infection, and autoimmune disease. The classical signal pathway of IL-33 includes the isotrimer of ST2 and interleukin-1 receptor accessory protein(IL-1 RAcP), which transduces signals into cells. The IL-33/ST2 signaling pathway affects bone metabolism by activating T and B lymphocytes. This article reviews the role of the IL-33/ST2 signaling pathway in bone metabolism. The results of a literature review showed that at present, scholars at home and abroad still dispute the role of IL-33 in bone metabolism. Some scholars believe that IL-33 can inhibit osteoclast formation, and IL-33 has been recently implicated in physiological bone remodeling. However, other scholars believe that IL-33 can promote osteoclast formation and differentiation, which leads to bone absorption. IL-33 and its signaling pathway are involved in bone metabolism of alveolar bone in periodontitis and periapical periodontitis. The specific mechanism remains unclear, and further studies are warranted.
引文
[1]Tseng CC,Huibers MM,Van Kuik JA,et al.The interleukin-33/ST2 pathway is expressed in the failing human heart and associated with pro-fibrotic remodeling of the myocardium[J].J Cardiovasc Transl Res,2018,11(1):15-21.
[2]Drake LY,Kita H.IL-33:biological properties,functions,and roles in airway disease[J].Immunol Rev,2017,278(1):173-184.
[3]Miller JE,Monsanto SP,Ahn SH,et al.Interleukin-33 modulates inflammation in endometriosis[J].Sci Rep,2017,7(1):17903.
[4]Ito T,Egusa C,Maeda T,et al.Stem cell factor suppressed IL-33-induced MHC classⅡexpression in murine bone marrow-derived mast cells[J].Allergol Int,2018,18:30115-30117.https://doi.org/10.1016/j.alit.2018.08.009.
[5]Macari S,Madeira M,Lima I,et al.ST2 regulates bone loss in a site-dependent and estrogen-dependent manner[J].J Cell Biochem,2018,119(10):8511-8521.
[6]Nile CJ,Barksby E,Jitprasertwong P,et al.Expression and regulation of interleukin-33 in human monocytes[J].Immunol,2010,130(2):172-180.
[7]Martin MU.Special aspects of interleukin-33 and the IL-33 receptor complex[J].Semin Immunol,2013,25(6):449-457.
[8]Lingel A,Weiss TM,Niebuhr M,et al.Structure of IL-33 and its interaction with the ST2 and IL-1RAcp receptors-insight into heterotrimeric IL-1 signaling complexes[J].Structure,2009,17(10):1398-1410.
[9]Palmer G,Lipsky BP,Smithgall MD,et al.The IL-1 receptor accessory protein(AcP)is required for IL-33 signaling and soluble AcP enhances the ability of soluble ST2 to inhibit IL-33[J].Cytokine,2008,42(3):358-364.
[10]孟欣,张晓敏,戴启刚,等.IL-33/ST2信号转导通路与过敏性鼻炎的研究进展[J].中华中医药杂志,2015,30(6):2032-2035.
[11]Zaiss MM,Kurowska-Stolarska M,B?hm C,et al.IL-33 shifts the balance from osteoclast to alternatively activated macrophage diff erentiation and protects from TNF-alpha-mediated bone loss[J].JImmunol,2011,186(11):6097-6105.
[12]Lima IL,Macari S,Madeira MF,et al.Osteoprotective effects of IL-33/ST2 link to osteociast apoptosis[J].Am J Pathol,2015,185(12):3338-3348.
[13]Mun SH,Ko NY,Kim HS,et al.Interleukin-33 stimulates formation of functional osteoclasts from human CD14 monocytes[J].Cell Mol Life Sci,2010,67(22):3883-3892.
[14]Yuichi M,Seicho M,Yu YC,et al.Involvement of ERK and p38MAPK pathways on interleukin-33-induced RANKL expression in osteoblastic cells[J].Cell Biol Int,2014,38(5):655-662.
[15]Saleh H,Eeles D,Hodge JM,et al.Interleukin-33,a target of parathyroid hormone and oncostatin M,increases osteoblastic matrix mineral deposition and inhibits osteoclast formation in vitro[J].Endocrinology,2011,152(5):1911-1922.
[16]Schulze J,Bickert T,Beil FT,et al.Interleukin-33 is expressed in differentiated osteoblasts and blocks osteoclast formation from bone marrow precursor cells[J].J Bone Miner Res,2011,26(4):704-717.
[17]Keller J,Catala-Lehnen P,Wintges K,et al.Transgenic over-expression of interleukin-33 in osteoblasts results in decreased osteoclastogenesis[J].Biochem Biophys Res Commu,2012,417(1):217-222.
[18]Kiyomiya H,Ariyoshi W,Okinaga TA,et al.IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression[J].Biochem Biophys Res Commun,2015,460(2):320-326.
[19]Felipe Andrés Cordero da Luz,Lima Ana Paula Oliveira,Borges D,et al.The physiopathological role of IL-33:new highlights in bone biology and a proposed role in periodontal disease[J].2014:342410.
[20]Malcolm J,Awang RA,Oliver-Bell J,et al.IL-33 exacerbates periodontal disease through induction of RANKL[J].J Dent Res,2015,94(7):968-975.
[21]Koseoglu S,Hatipoglu M,Saglam M,et al.Interleukin-33 could play an important role in the pathogenesis of periodontitis[J].JPeriodontal Res,2015,50(4):525-534.
[22]Velickovic M,Pejnovic N,Mitrovic SA,et al.ST2 deletion increases inflammatory bone destruction in experimentally induced periapical lesions in mice[J].J Endod,2015,41(3):369-375.(编辑张琳,曾曙光)
[2]Drake LY,Kita H.IL-33:biological properties,functions,and roles in airway disease[J].Immunol Rev,2017,278(1):173-184.
[3]Miller JE,Monsanto SP,Ahn SH,et al.Interleukin-33 modulates inflammation in endometriosis[J].Sci Rep,2017,7(1):17903.
[4]Ito T,Egusa C,Maeda T,et al.Stem cell factor suppressed IL-33-induced MHC classⅡexpression in murine bone marrow-derived mast cells[J].Allergol Int,2018,18:30115-30117.https://doi.org/10.1016/j.alit.2018.08.009.
[5]Macari S,Madeira M,Lima I,et al.ST2 regulates bone loss in a site-dependent and estrogen-dependent manner[J].J Cell Biochem,2018,119(10):8511-8521.
[6]Nile CJ,Barksby E,Jitprasertwong P,et al.Expression and regulation of interleukin-33 in human monocytes[J].Immunol,2010,130(2):172-180.
[7]Martin MU.Special aspects of interleukin-33 and the IL-33 receptor complex[J].Semin Immunol,2013,25(6):449-457.
[8]Lingel A,Weiss TM,Niebuhr M,et al.Structure of IL-33 and its interaction with the ST2 and IL-1RAcp receptors-insight into heterotrimeric IL-1 signaling complexes[J].Structure,2009,17(10):1398-1410.
[9]Palmer G,Lipsky BP,Smithgall MD,et al.The IL-1 receptor accessory protein(AcP)is required for IL-33 signaling and soluble AcP enhances the ability of soluble ST2 to inhibit IL-33[J].Cytokine,2008,42(3):358-364.
[10]孟欣,张晓敏,戴启刚,等.IL-33/ST2信号转导通路与过敏性鼻炎的研究进展[J].中华中医药杂志,2015,30(6):2032-2035.
[11]Zaiss MM,Kurowska-Stolarska M,B?hm C,et al.IL-33 shifts the balance from osteoclast to alternatively activated macrophage diff erentiation and protects from TNF-alpha-mediated bone loss[J].JImmunol,2011,186(11):6097-6105.
[12]Lima IL,Macari S,Madeira MF,et al.Osteoprotective effects of IL-33/ST2 link to osteociast apoptosis[J].Am J Pathol,2015,185(12):3338-3348.
[13]Mun SH,Ko NY,Kim HS,et al.Interleukin-33 stimulates formation of functional osteoclasts from human CD14 monocytes[J].Cell Mol Life Sci,2010,67(22):3883-3892.
[14]Yuichi M,Seicho M,Yu YC,et al.Involvement of ERK and p38MAPK pathways on interleukin-33-induced RANKL expression in osteoblastic cells[J].Cell Biol Int,2014,38(5):655-662.
[15]Saleh H,Eeles D,Hodge JM,et al.Interleukin-33,a target of parathyroid hormone and oncostatin M,increases osteoblastic matrix mineral deposition and inhibits osteoclast formation in vitro[J].Endocrinology,2011,152(5):1911-1922.
[16]Schulze J,Bickert T,Beil FT,et al.Interleukin-33 is expressed in differentiated osteoblasts and blocks osteoclast formation from bone marrow precursor cells[J].J Bone Miner Res,2011,26(4):704-717.
[17]Keller J,Catala-Lehnen P,Wintges K,et al.Transgenic over-expression of interleukin-33 in osteoblasts results in decreased osteoclastogenesis[J].Biochem Biophys Res Commu,2012,417(1):217-222.
[18]Kiyomiya H,Ariyoshi W,Okinaga TA,et al.IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression[J].Biochem Biophys Res Commun,2015,460(2):320-326.
[19]Felipe Andrés Cordero da Luz,Lima Ana Paula Oliveira,Borges D,et al.The physiopathological role of IL-33:new highlights in bone biology and a proposed role in periodontal disease[J].2014:342410.
[20]Malcolm J,Awang RA,Oliver-Bell J,et al.IL-33 exacerbates periodontal disease through induction of RANKL[J].J Dent Res,2015,94(7):968-975.
[21]Koseoglu S,Hatipoglu M,Saglam M,et al.Interleukin-33 could play an important role in the pathogenesis of periodontitis[J].JPeriodontal Res,2015,50(4):525-534.
[22]Velickovic M,Pejnovic N,Mitrovic SA,et al.ST2 deletion increases inflammatory bone destruction in experimentally induced periapical lesions in mice[J].J Endod,2015,41(3):369-375.(编辑张琳,曾曙光)