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Interleukin-23 Secreted by Activated Macrophages Drives ??T Cell Production of Interleukin-17 to Aggravate Secondary Injury After Intracerebral Hemorrhage.

ABSTRACT:

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 ??T-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 TLR2/TLR4 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.

SUBMITTER: Zhong Q

PROVIDER: S-EPMC5121525 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Interleukin-23 Secreted by Activated Macrophages Drives γδT Cell Production of Interleukin-17 to Aggravate Secondary Injury After Intracerebral Hemorrhage.

Zhong Qi Q Zhou Kai K Liang Qiao-Li QL Lin Sen S Wang Yan-Chun YC Xiong Xiao-Yi XY Meng Zhao-You ZY Zhao Ting T Zhu Wen-Yao WY Yang Yuan-Rui YR Liao Mao-Fan MF Gong Qiu-Wen QW Liu Liang L Xiong Ao A Hao Junwei J Wang Jian J Yang Qing-Wu QW

Journal of the American Heart Association 20161011 10

<h4>Background</h4>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.<h4>Methods and results</h4>Our results showed that peripheral macrophages and T lymphocytes ...[more]

PMID: 27729335

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