Details

Autor(en) / Beteiligte

• Xu, Xiupeng
• Zhi, Tongle
• Hua, Lingyang
• Jiang, Kuan
• Chen, Chen

Titel

IRAK4 exacerbates traumatic brain injury via activation of TAK1 signaling pathway

Ist Teil von

• Experimental neurology, 2022-05, Vol.351, p.114007-114007, Article 114007

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Although multiple signaling pathways contributing to the pathophysiological process have been investigated, treatments for traumatic brain injury (TBI) against present targets have not acquired significant clinical progress. Interleukin-1 receptor-associated kinase 4 (IRAK4) is an important factor involved in regulating immunity and inflammation. However, the role of IRAK4 in TBI still remains largely unknown. Therefore, using a controlled cortical impact model (CCI), we investigated the function and molecular mechanism of IRAK4 in the context of TBI. IRAK4 was found to be activated in a time-dependent manner after TBI and mainly expressed in neurons. Inhibition of IRAK4 by siRNAs could significantly alleviates neuroinflammation, neuron apoptosis, brain edema, brain-blood barrier (BBB) dysfunction and improves neurological deficit in the context of CCI. Mechanistically, IRAK4 exacerbates CCI via activation of TAK1 signaling pathway. Interestingly, PF-0665083, an IRAK4 inhibitor, inhibits phosphorylation of IRAK4 and attenuates CCI-induced secondary injury. It could be conclude that IRAK4 plays a critical role in TBI-induced secondary injury and the underlining mechanism may be related to activation of TAK1 signaling pathway. PF-0665083 may serve as a potential treatment strategy to relieve TBI. •p-IRAK4 and IRAK4 expressions were upregulated in pericontusional cortex after TBI.•Inhibition of IRAK4 exerted neuroprotective effects on CCI-induced secondary injuries.•IRAK4 exacerbated CCI via activation of TAK1 signaling pathway.•PF-06650833 exerted neuroprotective effects on CCI-induced secondary injury by regulating IRAK4/TAK1 signaling pathway.