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

Xinchun Ye, Delian Kong, Jun Wang, Tauheed Ishrat, Hongjuan Shi, Xiaohui Ding, Guiyun Cui, Fang Hua

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)69-74
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume480
Issue number1
DOIs
StatePublished - Nov 4 2016

Fingerprint

NF-kappa B
Brain Ischemia
Reperfusion
Toll-Like Receptors
Chemical activation
Knockout Mice
Interferons
Brain
Myeloid Differentiation Factor 88
Interferon-beta
Cyclooxygenase 2
Reperfusion Injury
Interleukin-1
Vascular Endothelial Growth Factor A
Real-Time Polymerase Chain Reaction
Interleukin-6
Proteins
Western Blotting
Enzyme-Linked Immunosorbent Assay
Tissue

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

MyD88 contributes to neuroinflammatory responses induced by cerebral ischemia/reperfusion in mice. / Ye, Xinchun; Kong, Delian; Wang, Jun; Ishrat, Tauheed; Shi, Hongjuan; Ding, Xiaohui; Cui, Guiyun; Hua, Fang.

In: Biochemical and Biophysical Research Communications, Vol. 480, No. 1, 04.11.2016, p. 69-74.

Research output: Contribution to journalArticle

Ye, Xinchun ; Kong, Delian ; Wang, Jun ; Ishrat, Tauheed ; Shi, Hongjuan ; Ding, Xiaohui ; Cui, Guiyun ; Hua, Fang. / MyD88 contributes to neuroinflammatory responses induced by cerebral ischemia/reperfusion in mice. In: Biochemical and Biophysical Research Communications. 2016 ; Vol. 480, No. 1. pp. 69-74.
@article{3abcc5fc07cc4181bc50c37ec0bb3a5f,
title = "MyD88 contributes to neuroinflammatory responses induced by cerebral ischemia/reperfusion in mice",
abstract = "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.",
author = "Xinchun Ye and Delian Kong and Jun Wang and Tauheed Ishrat and Hongjuan Shi and Xiaohui Ding and Guiyun Cui and Fang Hua",
year = "2016",
month = "11",
day = "4",
doi = "10.1016/j.bbrc.2016.10.007",
language = "English (US)",
volume = "480",
pages = "69--74",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - MyD88 contributes to neuroinflammatory responses induced by cerebral ischemia/reperfusion in mice

AU - Ye, Xinchun

AU - Kong, Delian

AU - Wang, Jun

AU - Ishrat, Tauheed

AU - Shi, Hongjuan

AU - Ding, Xiaohui

AU - Cui, Guiyun

AU - Hua, Fang

PY - 2016/11/4

Y1 - 2016/11/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84992189468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992189468&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2016.10.007

DO - 10.1016/j.bbrc.2016.10.007

M3 - Article

VL - 480

SP - 69

EP - 74

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 1

ER -