Open AccessInterleukin‐23 Secreted by Activated Macrophages Drives γδT Cell Production of Interleukin‐17 to Aggravate Secondary Injury After Intracerebral Hemorrhage
Author(s) -
Zhong Qi,
Zhou Kai,
Liang QiaoLi,
Lin Sen,
Wang YanChun,
Xiong XiaoYi,
Meng ZhaoYou,
Zhao Ting,
Zhu WenYao,
Yang YuanRui,
Liao MaoFan,
Gong QiuWen,
Liu Liang,
Xiong Ao,
Hao Junwei,
Wang Jian,
Yang QingWu
Publication year - 2016
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.116.004340
Subject(s) - medicine , proinflammatory cytokine , intracerebral hemorrhage , neuroinflammation , tlr2 , immunology , inflammation , tumor necrosis factor alpha , interleukin , tlr4 , pathology , cytokine , subarachnoid hemorrhage
Background Neuroinflammation plays a key role in intracerebral hemorrhage ( ICH )–induced secondary brain injury, but the specific roles of peripheral inflammatory cells such as macrophages and lymphocytes remain unknown. The purpose of this study was to explore the roles of macrophages, T lymphocytes, and the cytokines they secrete as potential targets for treating secondary brain injury after ICH . Methods and Results Our results showed that peripheral macrophages and T lymphocytes successively infiltrated the brain, with macrophage counts peaking 1 day after ICH and T‐lymphocyte counts peaking after 4 days. These peaks in cellular infiltration corresponded to increases in interleukin ( IL )‐23 and IL ‐17 expression, respectively. We found that hemoglobin from the hematoma activated IL ‐23 secretion by infiltrating macrophages by inducing the formation of toll‐like receptor (TLR) 2/4 heterodimer. This increased IL ‐23 expression stimulated γδT‐cell production of IL ‐17, which increased brain edema and neurologic deficits in the model mice as a proinflammatory factor. Finally, we found that sparstolonin B (SsnB) could ameliorate brain edema and neurologic deficits in ICH model mice via inhibition of TLR 2/ TLR 4 heterodimer formation, and notably, SsnB interacted with myeloid differentiation factor 88 Arg196. Conclusions Together, our results reveal the importance of the IL ‐23/ IL ‐17 inflammatory axis in secondary brain injury after ICH and thus provide a new therapeutic target for ICH treatment.