Toll‐like receptor 2/4 heterodimer mediates inflammatory injury in intracerebral hemorrhage

Wang, Yanchun; Zhou, Yu; Huang, Feizhou; Su, Lin; Wang, Pengfei; Xiong, Ranhua; Chen, Jing; Xiong, Xiao‐Yi; Lv, Fenglin; Liang, Qiaoli; Yang, Qingwu

doi:10.1002/ana.24159

Cited by 132 publications

(143 citation statements)

References 33 publications

Supporting

Mentioning

141

Contrasting

Order By: Relevance

“…These specific genes function in efferocytosis and in the inhibition of cytokine responses (Axl), phagolysosome formation (Lamp1 and Cd63) and lipid efflux (Abcg1) (41,42). Clustering very closely were bin and TLR4 activation are critical initiators of the inflammatory response after ICH (30,(46)(47)(48)(49)(50)(51). After stimulation, bone marrowderived macrophages (BMDMs) were incubated with fluorescently labeled heat-shocked erythrocytes that externalized PtdSer ( Figure 3B).…”

Section: Resultsmentioning

confidence: 99%

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

Chang¹,

Goods²,

Askenase³

et al. 2017

Journal of Clinical Investigation

140

161

View full text Add to dashboard Cite

-/-bone marrow chimeras (BMCs) at days 7 and 15 after ICH. Right: Quantification of residual hematoma volume in the WT and Ccr2 -/-BMCs. n = 11 at day 7; n = 9 at day 15. *P < 0.05 by Student's t test. (B) Cylinder test and apomorphine turning test from WT and Ccr2 -/-BMCs at day 15 after ICH. n = 6/group for cylinder test; n = 8/ group for apomorphine turning test. *P < 0.05 by Student's t test. (C) Cylinder test, neurological deficit score, and corner test in control-and anti-CCR2 antibody-treated mice at days 1 and 3 after collagenase ICH. n = 7/group. *P < 0.05 by 1-way repeated-measures ANOVA and Bonferroni's post hoc test. (D) Top: Representative coronal sections show hematoma from control-and anti-CCR2 antibody-treated WT mice after blood injection ICH at 7 days. Bottom: Quantification of hematoma volume, n = 3/ group. *P < 0.05 versus control by Student's t test. (E) Top: Representative coronal sections show hematoma in the isotype control-and anti-CCR2 antibody-treated mice from collagenase model at day 12. Bottom: Quantification of hematoma volume. n = 8/group. *P < 0.05 versus control by Student's t test. (F) The cylinder test, neurological deficit score, and corner test in isotype control-and anti-CCR2 antibody-treated ICH mice at days 3, 5, 7, 9, and 11 after collagenase ICH surgery. n = 8/group. *P < 0.05 versus isotype control group by 1-way repeated-measures ANOVA and Bonferroni's post hoc test. αCCR2, anti-CCR2 antibody.

show abstract

Section: Resultsmentioning

confidence: 99%

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

Chang¹,

Goods²,

Askenase³

et al. 2017

Journal of Clinical Investigation

140

161

View full text Add to dashboard Cite

show abstract

“…TLR/IL-1R, IL-17R, and TCR signaling may participate in this process (33)(34)(35)(36)(37). Our experiments mainly focused on TRAF6, which is downstream of inflammatory pathways, but the signaling that is initiated and mediated by TLRs/IL-1R, IL-17R, and the TCR requires further study.…”

Section: /2mentioning

confidence: 99%

A20 Ameliorates Intracerebral Hemorrhage–Induced Inflammatory Injury by Regulating TRAF6 Polyubiquitination

Meng

Zhao

Zhou

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

Reducing excessive inflammation is beneficial for the recovery from intracerebral hemorrhage (ICH). Here, the roles and mechanisms of A20 (TNFAIP3), an important endogenous anti-inflammatory factor, are examined in ICH. A20 expression in the PBMCs of ICH patients and an ICH mouse model was detected, and the correlation between A20 expression and neurologic deficits was analyzed. A20 expression was increased in PBMCs and was negatively related to the modified Rankin Scale score. A20 expression was also increased in mouse perihematomal tissues. A20−/− and A20-overexpressing mice were generated to further analyze A20 function. Compared with wild-type (WT) mice, A20−/− and A20-overexpressing mice showed significant increases and decreases, respectively, in hematoma volume, neurologic deficit score, mortality, neuronal degeneration, and proinflammatory factors. Moreover, WT-A20−/− parabiosis was established to explore the role of A20 in peripheral blood in ICH injury. ICH-induced damage, including brain edema, neurologic deficit score, proinflammatory factors, and neuronal apoptosis, was reduced in A20−/− parabionts compared with A20−/− mice. Finally, the interactions between TRAF6 and Ubc13 and UbcH5c were increased in A20−/− mice compared with WT mice; the opposite occurred in A20-overexpressing mice. Enhanced IκBα degradation and NF-κB activation were observed in A20−/− mice, but the results were reversed in A20-overexpressing mice. These results suggested that A20 is involved in regulating ICH-induced inflammatory injury in both the central and peripheral system and that A20 reduces ICH-induced inflammation by regulating TRAF6 polyubiquitination. Targeting A20 may thus be a promising therapeutic strategy for ICH.

show abstract

“…Secondary brain injury following ICH includes hematoma toxicity, high metabolic injury, excitotoxicity, oxidative stress and inflammatory injury (1,(9)(10)(11). Previous studies into injury following ICH have focused downstream of inflammation and have not identified reagents that induce sufficient therapeutic effects in patients with ICH (5,8).…”

Section: Discussionmentioning

confidence: 99%

“…Toll-like receptors (TLRs), which recognize distinct pathogen-and damage-associated molecular patterns, serve an important role in innate immunity and inflammatory responses (9,10). It has been demonstrated that TLR4 is involved in the inflammatory response that occurs following ICH, which subsequently activates nuclear factor (NF)-κB via the downstream myeloid differentiation primary response 88 (MyD88)/TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling pathway (11). Some natural compounds, including Curcumin (12) and Vitamin D (13), attenuated TLR4-induced inflammation injury in atherosclerosis and hyperoxia-induced lung injury.…”

Section: Introductionmentioning

confidence: 99%

Sparstolonin B improves neurological outcomes following intracerebral hemorrhage in mice

Wang¹,

Jiang²,

Xiao³

et al. 2018

Exp Ther Med

View full text Add to dashboard Cite

Abstract. Inflammation serves an important role in inducing secondary injury following intracerebral hemorrhage (ICH).It has been demonstrated that sparstolonin B (SsnB) is able to attenuate the lipopolysaccharide-induced inflammatory response in sepsis. Mouse ICH models were used to explore the efficacy of SsnB on the ICH-induced inflammatory response. Mice underwent a working memory version of Morris water maze (MWM) test. They underwent 5 successive days of training consisting of 4 trials each day. The ICH model was established on the last training day. Mice were injected intraperitoneally either with vehicle or SsnB once a day for 3 consecutive days following the establishment of the ICH model. The MWM was used to determine the effect of SsnB on short-term memory following ICH. Neurological deficit scores and brain water content were measured following the MWM. Furthermore, the expression of inflammatory factors and signaling molecules downstream of TLR4 were measured. The results demonstrated that 5 mg/kg SsnB significantly improved the MWM path and time latency (P<0.05). Furthermore, neurological deficit scores were decreased in SsnB-treated mice compared with vehicle-treated mice (P<0.01). Brain water content, levels of inflammatory cytokines and the expression of inflammation-associated proteins were also significantly reduced in the SsnB-treated group (P<0.05). These results indicate that SsnB treatment stimulates short-term neurobehavioral recovery and reduces neurological deficits and this may inhibit the inflammatory response. Therefore, SsnB may attenuate the inflammatory response following ICH.

show abstract

Toll‐like receptor 2/4 heterodimer mediates inflammatory injury in intracerebral hemorrhage

Abstract: Our results suggest that a novel TLR2/TLR4 heterodimer induced by Hb initiates inflammatory injury in ICH. Interfering with the assembly of the TLR2/TLR4 heterodimer may be a novel target for developing effective treatment of ICH.

Cited by 132 publications

References 33 publications

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

A20 Ameliorates Intracerebral Hemorrhage–Induced Inflammatory Injury by Regulating TRAF6 Polyubiquitination

Sparstolonin B improves neurological outcomes following intracerebral hemorrhage in mice

Contact Info

Product

Resources

About