MyD88 contributes to neuroinflammatory responses induced by cerebral ischemia/reperfusion in mice

Journal Article · Fri Nov 04 04:00:00 EDT 2016 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2016.10.007· OSTI ID:22696679

Ye, Xinchun; Kong, Delian ^[1]; Wang, Jun; Ishrat, Tauheed ^[2]; Shi, Hongjuan ^[1]; Ding, Xiaohui ^[3]; Cui, Guiyun ^[1]; Hua, Fang ^[1]

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1. Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002 (China)
2. Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA (United States)
3. Department of Human Anatomy, Histology and Embryology, Shenyang Medical College, Shenyang, 110000 (China)

Myeloid differentiation primary-response protein-88 (MyD88) is one of adaptor proteins mediating Toll-like receptors (TLRs) signaling. Activation of MyD88 results in the activation of nuclear factor kappa B (NFκB) and the increase of inflammatory responses. Evidences have demonstrated that TLRs signaling contributes to cerebral ischemia/reperfusion (I/R) injury. However, the role of MyD88 in this mechanism of action is disputed and needs to be clarified. In the present study, in a mouse model of cerebral I/R, we examined the activities of NFκB and interferon factor-3 (IRF3), and the inflammatory responses in ischemic brain tissue using ELISA, Western blots, and real-time PCR. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. Our results showed that NFκB activity increased in ischemic brains, but IRF3 was not activated after cerebral I/R, in wild-type (WT) mice. MyD88 deficit inhibited the activation of NFκB, and the expression of interleukin-1β (IL-1β), IL-6, Beclin-1 (BECN1), pellino-1, and cyclooxygenase-2 (COX-2) increased by cerebral I/R compared with WT mice. Interestingly, the expression of interferon Beta 1 (INFB1) and vascular endothelial growth factor (VEGF) increased in MyD88 KO mice. Unexpectedly, although the neurological function improved in the MyD88 knockout (KO) mice, the deficit of MyD88 failed to reduce cerebral infarct size compared to WT mice. We concluded that MyD88-dependent signaling contributes to the inflammatory responses induced by cerebral I/R. MyD88 deficit may inhibit the increased inflammatory response and increase neuroprotective signaling. - Highlights: • Cerebral ischemia/reperfusion activates inflammatory responses in brain tissue. • MyD88-dependent pathway contributes to the activated inflammatory responses. • MyD88 deficit increases neuroprotective signaling in ischemic brain.

• OSTI ID: 22696679
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 480; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BRAIN
ENZYME IMMUNOASSAY
INFLAMMATION
ISCHEMIA
KNOCK-OUT REACTIONS
MICE
PLANT GROWTH
POLYMERASE CHAIN REACTION
SIGNALS