title: IL-33 Exerts Neuroprotective Effect in Mice Intracerebral Hemorrhage Model Through Suppressing Inflammation/Apoptotic/Autophagic Pathway.
abstract: Interleukin-33 (IL-33) is a recently identified member of the IL-1 family that exerts biologic functions by binding to a heterodimer composed of IL-1 receptor-related protein ST2L and IL-1RAcP. However, the role of IL-33 and whether IL-33 accounts for inflammation, apoptotic, and autophagic neuropathology after intracerebral hemorrhage (ICH) are not clear. Here, we established a mouse ICH model in this study, to determine the role of IL-33 and explore the underlying mechanism. Male mice were subjected to an infusion of type IV collagenase/saline into the left striatum to induce ICH/sham model. IL-33, soluble ST2 (sST2), or saline were also administered by a single intracerebroventricular (i.c.v.) injection, respectively. The results showed that the expression level of IL-33 markedly decreased within 6 h and reached the valleys at 6 and 72 h after ICH vs. sham group. In parallel, ST2L (a transmembrane form receptor of IL-33) significantly increased within 6 h and reached the peaks at 6 h and 24 h after ICH vs. sham group. In addition, administration of IL-33 alleviated cerebral water contents, reduced the number of PI- and TUNEL-positive cells, and improved neurological function after ICH. Moreover, IL-33 treatment apparently suppressed the expression of pro-inflammation cytokines IL-1β and TNF-α, evidently increased Bcl-2 but decreased cleaved-caspase-3, and obviously decreased the levels of autophagy-associated proteins LC3-II and Beclin-1 but maintained P62 at high level after ICH. On the contrary, treatment with sST2, a decoy receptor of IL-33, exacerbated ICH-induced brain damage and neurological dysfunction by promoting apoptosis, and enhancing autophagic activity. In conclusion, IL-33 provides neuroprotection through suppressing inflammation, apoptotic, and autophagic activation in collagenase-induced ICH model.
authors.affiliation: Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China.
authors.forename: Cheng-Liang
authors.initials: CL
authors.lastname: Luo
authors.affiliation: Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Zhang
authors.affiliation: Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Meng
authors.affiliation: Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Ji
authors.affiliation: Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China.
authors.forename: Zu-Feng
authors.initials: ZF
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China. xiping.chen@163.com.
authors.forename: Xi-Ping
authors.initials: XP
authors.lastname: Chen
authors.affiliation: Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China. taoluyang@suda.edu.cn.
authors.forename: Lu-Yang
authors.initials: LY
authors.lastname: Tao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000188:drug therapy*; D017364:Collagenases / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D000067596:Interleukin-33 / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D000067596:Interleukin-33; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017472:Receptors, Interleukin-1; C530318:ST2L protein, mouse; D053148:Caspase 3; D017364:Collagenases
keywords: Apoptosis; Autophagy; Inflammation; Interleukin-33; Intracerebral hemorrhage; ST2