Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats
Background and purpose: Ischemic stroke activates Toll-like receptors (TLRs), triggering rapid inflammatory cytokine production. Axl signaling has multiple roles, including regulating cytokine secretion, clearing apoptotic cells, and maintaining cell survival, however, its role in inflammation after...
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doaj-6db397399a2c4213b13a886c71be138a2021-03-22T12:46:01ZengElsevierNeurobiology of Disease1095-953X2018-02-011105967Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in ratsGuangyong Wu0Devin W. McBride1John H. Zhang2Departments of Anesthesiology, Physiology & Pharmacology, Loma Linda University, Loma Linda, CA, USA; Department of Neurosurgery, the Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartments of Anesthesiology, Physiology & Pharmacology, Loma Linda University, Loma Linda, CA, USADepartments of Anesthesiology, Physiology & Pharmacology, Loma Linda University, Loma Linda, CA, USA; Corresponding author: Department of Anesthesiology, Loma Linda University School of Medicine, 11041 Campus Street, Loma Linda, CA 92354, U.S.A.Background and purpose: Ischemic stroke activates Toll-like receptors (TLRs), triggering rapid inflammatory cytokine production. Axl signaling has multiple roles, including regulating cytokine secretion, clearing apoptotic cells, and maintaining cell survival, however, its role in inflammation after ischemic stroke has not been examined. We hypothesized that activation of Axl by recombinant Growth-arrest-specific protein 6 (rGas6) attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after middle cerebral artery occlusion (MCAO) in rats. Meth: Sprague-Dawley rats were subjected to 2h of MCAO. One hour after reperfusion, the rats were given an intranasal injection of rGas6, vehicle, or R428 (Axl receptor inhibitor). Neurological scores, infarct volumes, immunofluorescence staining, Morris Water Maze, rotarod test and histology alterations were analyzed. The expressions of proinflammatory cytokines, including IL-1β, IL-6, TNF-α, and Gas6, Axl, STAT1, SOCS1, SOCS3 and the TLR/TRAF/NF-κB pathway were quantified using Western blot. Results: Endogenous expressions of Gas6 and Axl decreased significantly by 24h after MCAO. rGas6 reduced brain infarction and improved neurologic deficits scores, and increased expression of Axl and decreased the expressions of TRAF3, TRAF6 and inflammatory factors IL-1β, IL-6, and TNF-α. Four weeks after MCAO, rGas6 improved long-term neurological behavior and memory. Inhibition of the Axl/TLR/TRAF/NF-κB pathway reversed the brain protection by rGas6. Conclusion: rGas6 reduced the neurological deficits by inhibiting neuroinflammation via the TLR/TRAF/NF-κB signaling pathway. rGas6 can be used as potential treatment to ischemic stroke.http://www.sciencedirect.com/science/article/pii/S0969996117302693Growth-arrest-specific protein 6AxlToll-like receptorInflammationMiddle cerebral artery occlusion |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guangyong Wu Devin W. McBride John H. Zhang |
spellingShingle |
Guangyong Wu Devin W. McBride John H. Zhang Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats Neurobiology of Disease Growth-arrest-specific protein 6 Axl Toll-like receptor Inflammation Middle cerebral artery occlusion |
author_facet |
Guangyong Wu Devin W. McBride John H. Zhang |
author_sort |
Guangyong Wu |
title |
Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats |
title_short |
Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats |
title_full |
Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats |
title_fullStr |
Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats |
title_full_unstemmed |
Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats |
title_sort |
axl activation attenuates neuroinflammation by inhibiting the tlr/traf/nf-κb pathway after mcao in rats |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2018-02-01 |
description |
Background and purpose: Ischemic stroke activates Toll-like receptors (TLRs), triggering rapid inflammatory cytokine production. Axl signaling has multiple roles, including regulating cytokine secretion, clearing apoptotic cells, and maintaining cell survival, however, its role in inflammation after ischemic stroke has not been examined. We hypothesized that activation of Axl by recombinant Growth-arrest-specific protein 6 (rGas6) attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after middle cerebral artery occlusion (MCAO) in rats. Meth: Sprague-Dawley rats were subjected to 2h of MCAO. One hour after reperfusion, the rats were given an intranasal injection of rGas6, vehicle, or R428 (Axl receptor inhibitor). Neurological scores, infarct volumes, immunofluorescence staining, Morris Water Maze, rotarod test and histology alterations were analyzed. The expressions of proinflammatory cytokines, including IL-1β, IL-6, TNF-α, and Gas6, Axl, STAT1, SOCS1, SOCS3 and the TLR/TRAF/NF-κB pathway were quantified using Western blot. Results: Endogenous expressions of Gas6 and Axl decreased significantly by 24h after MCAO. rGas6 reduced brain infarction and improved neurologic deficits scores, and increased expression of Axl and decreased the expressions of TRAF3, TRAF6 and inflammatory factors IL-1β, IL-6, and TNF-α. Four weeks after MCAO, rGas6 improved long-term neurological behavior and memory. Inhibition of the Axl/TLR/TRAF/NF-κB pathway reversed the brain protection by rGas6. Conclusion: rGas6 reduced the neurological deficits by inhibiting neuroinflammation via the TLR/TRAF/NF-κB signaling pathway. rGas6 can be used as potential treatment to ischemic stroke. |
topic |
Growth-arrest-specific protein 6 Axl Toll-like receptor Inflammation Middle cerebral artery occlusion |
url |
http://www.sciencedirect.com/science/article/pii/S0969996117302693 |
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