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IL-33 Exerts Neuroprotective Effect in Mice Intracerebral Hemorrhage Model Through Suppressing Inflammation/Apoptotic/Autophagic Pathway

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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.

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Acknowledgments

This study was supported by grants 81271379, 81373251, and 81530062 from the National Natural Science Foundation of China, National High Technology Research and Development Program of China (863 Program, No.2015AA020503), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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    1. Department of Forensic Medicine, Medical School of Soochow University, 178 Ganjiang East Road, Suzhou, 215123, China

      Yuan Gao, Lu Ma, Cheng-liang Luo, Tao Wang, Ming-yang Zhang, Xi Shen, Huan-huan Meng, Meng-meng Ji, Zu-feng Wang, Xi-ping Chen & Lu-yang Tao

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    Gao, Y., Ma, L., Luo, Cl. et al. IL-33 Exerts Neuroprotective Effect in Mice Intracerebral Hemorrhage Model Through Suppressing Inflammation/Apoptotic/Autophagic Pathway. Mol Neurobiol 54, 3879–3892 (2017). https://doi.org/10.1007/s12035-016-9947-6

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