CD11b-activated Src signal attenuates neuroinflammatory pain by orchestrating inflammatory and anti-inflammatory cytokines in microglia

Yang, Mei; Xu, Wenyun; Wang, Yiru; Jiang, Xin; Li, Yingke; Yang, Yajuan; Yuan, Hong

doi:10.1177/1744806918808150

Cited by 17 publications

(13 citation statements)

References 45 publications

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“…Because a heterogeneous population has been transplanted to hydrocephalic hyh mice, more than one effect is expected. In this way, 10% of MSC were positive for CD11b, a molecule that inhibits TLR-induced inflammatory responses by the inhibition of inflammatory cytokines (IL-6 and TNFα) and increasing anti-inflammatory cytokine (IL-10 and TGF-β) production in microglia [56]. This suggests that part of the transplanted cells could have an anti-inflammatory role.…”

Section: Neuroprotective Effect Of Bm-msc In Hydrocephalic Micementioning

confidence: 95%

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

et al. 2020

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Background: In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model. Methods: BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and nonhydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using 1 H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1 H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay.

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Section: Neuroprotective Effect Of Bm-msc In Hydrocephalic Micementioning

confidence: 95%

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

et al. 2020

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“…Similarly, immunoblotting analyses reveled no differences in extracellular signal-regulated kinase (ERK) activation (phosphorylation) between WT and MPO KO PMNs (Supplemental Figure 2D). ERK plays an important role in PMN chemotaxis (28) and can be activated downstream of CD11b (29).…”

Section: Cd11b Surface Expression Is Not Altered By the Absence Of Mpomentioning

confidence: 99%

Released Myeloperoxidase Attenuates Neutrophil Migration and Accumulation in Inflamed Tissue

et al. 2021

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Neutrophil (PMN) recruitment to sites of insult is critical for host defense, however excessive PMN activity and tissue accumulation can lead to exacerbated inflammation and injury. Myeloperoxidase (MPO) is a PMN azurophilic granule enzyme, which together with H2O2, forms a powerful antimicrobial system designed to kill ingested bacteria. Intriguingly, in addition to intracellular killing of invading microorganisms and extracellular tissue damage due generation of ROS, soluble MPO has been directly implicated in modulating cellular responses and tissue homeostasis. In the current work, we used several models of inflammation, murine and human PMNs and state-of-the-art intravital microscopy to examine the effect of MPO on PMN migration and tissue accumulation. We found that in the absence of functional MPO (MPO knockout, KO mice) inflammatory PMN tissue accumulation was significantly enhanced. We determined that the elevated numbers of PMNs in MPO knockout mice was not due to enhanced viability, but due to increased migratory ability. Acute PMN migration in models of zymosan-induced peritonitis or ligated intestinal loops induced by intraluminal administration of PMN-chemokine CXCL1 was increased over 2-fold in MPO KO compared to wild type (WT) mice. Using real-time intravital imaging of inflamed mouse cremaster muscle and ex vivo PMN co-culture with inflamed endothelial cells (ECs) we demonstrate that elevated migration of MPO KO mice was due to enhanced adhesive interactions. In contrast, addition of soluble recombinant MPO both in vivo and ex vivo diminished PMN adhesion and migration. Although MPO has been previously suggested to bind CD11b, we found no significant difference in CD11b expression in either resting or activated PMNs and further showed that the MPO binding to the PMN surface is not specific to CD11b. As such, our data identify MPO as a novel regulator of PMN trafficking in inflammation.

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“…Our results indicate that the expression of CD11b was weaker than Iba1 ( Figure 7 and Figure 8 ), which led to the subsequent dominance of Iba1+/CD11b− microglial cells in alcoholics in both gray and white matter in SNpr and SNpc (up to 40–50% of all microglial/macrophage population). Previous studies in mice-brain-derived microglial cells have demonstrated that CD11b silences TLR4 (toll-like receptor 4) -induced inflammatory responses [ 89 ]. Such physiological silencing in controls (wild-type mice) leads to increased microglial production of IL-10 and TGF-β (anti-inflammatory cytokines), coupled with decreased production of IL-6 and TNF-α (pro-inflammatory cytokines) [ 89 ], thereby indicating that silencing of CD11b promotes a pro-inflammatory microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Chronic Alcoholism and HHV-6 Infection Synergistically Promote Neuroinflammatory Microglial Phenotypes in the Substantia Nigra of the Adult Human Brain

et al. 2021

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Both chronic alcoholism and human herpesvirus-6 (HHV-6) infection have been identified as promoters of neuroinflammation and known to cause movement-related disorders. Substantia Nigra (SN), the dopaminergic neuron-rich region of the basal ganglia, is involved in regulating motor function and the reward system. Hence, we hypothesize the presence of possible synergism between alcoholism and HHV-6 infection in the SN region and report a comprehensive quantification and characterization of microglial functions and morphology in postmortem brain tissue from 44 healthy, age-matched alcoholics and chronic alcoholics. A decrease in the perivascular CD68+ microglia in alcoholics was noted in both the gray and white matter. Additionally, the CD68+/Iba1− microglial subpopulation was found to be the dominant type in the controls. Conversely, in alcoholics, dystrophic changes in microglia were seen with a significant increase in Iba1 expression and perivascular to diffuse migration. An increase in CD11b expression was noted in alcoholics, with the Iba1+/CD11b− subtype promoting inflammation. All the controls were found to be negative for HHV-6 whilst the alcoholics demonstrated HHV-6 positivity in both gray and white matter. Amongst HHV-6 positive alcoholics, all the above-mentioned changes were found to be heightened when compared with HHV-6 negative alcoholics, thereby highlighting the compounding relationship between alcoholism and HHV-6 infection that promotes microglia-mediated neuroinflammation.

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CD11b-activated Src signal attenuates neuroinflammatory pain by orchestrating inflammatory and anti-inflammatory cytokines in microglia

Cited by 17 publications

References 45 publications

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

Released Myeloperoxidase Attenuates Neutrophil Migration and Accumulation in Inflamed Tissue

Chronic Alcoholism and HHV-6 Infection Synergistically Promote Neuroinflammatory Microglial Phenotypes in the Substantia Nigra of the Adult Human Brain

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