title: Matrine downregulates IL-33/ST2 expression in the central nervous system of rats with experimental autoimmune encephalomyelitis.
abstract: Interleukin (IL)-33 is a recently described member of the IL-1 family and functions as a ligand for ST2, a member of the IL-1 receptor family. The role of IL-33/ST2 axis in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS), remains controversial. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to suppress clinical EAE and CNS inflammation. However, the underlying immunoregulatory mechanisms have not been fully elucidated, and whether this effect of MAT is through inhibiting the function of the IL-33/ST2 axis is not known. In this study, we investigated the relationship between the therapeutic effects of MAT and IL-33/ST2 expression. MAT treatment successfully attenuated severe clinical deficit and histopathological changes, compared to untreated controls. While IL-33/ST2 mRNA expression was largely increased in spinal cord of EAE rats compared to naïve rats, this expression was significantly inhibited in rats treated with MAT. These results were further confirmed by their protein levels tested with immunohistochemistry. Together, our study demonstrates that MAT treatment regulates the inflammatory IL-33/ST2 axis, thus being a novel mechanism underlying the effect of MAT.
authors: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Xiaoyu
authors: X
authors: Zhao
authors: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Xiaojian
authors: X
authors: Zhang
authors: Department of Nutriology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Ying
authors: Y
authors: Lv
authors: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Yuming
authors: Y
authors: Xu
authors: Department of Neurosurgery, Nanshi Affiliated Hospital of Henan University, Nanyang 473000, Henan, China.
authors: Menglong
authors: M
authors: Li
authors: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Qingxia
authors: Q
authors: Pan
authors: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Yaojuan
authors: Y
authors: Chu
authors: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Nan
authors: N
authors: Liu
authors: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: Guang-Xian.Zhang@jefferson.edu.
authors: Guang-Xian
authors: GX
authors: Zhang
authors: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: zhulin66zhulin@126.com.
authors: Lin
authors: L
authors: Zhu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D002490:Central Nervous System / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D000067596:Interleukin-33 / Q000235:genetics* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology*; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000871:Anthelmintics; D000067596:Interleukin-33; D011807:Quinolizines; D017472:Receptors, Interleukin-1; C000589812:ST2 protein, rat; D000093842:Matrines
keywords: Experimental autoimmune encephalomyelitis; IL-33; Matrine; Multiple sclerosis; ST2