Interleukin-10 attenuates impairment of the blood-brain barrier in a severe acute pancreatitis rat model

Lin, Ronggui; Chen, Fei; Su, Wen Pang; Teng, Tianhong; Pan, Yu; Huang, Heguang

doi:10.1186/s12950-018-0180-0

Cited by 44 publications

(31 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vascular remodeling may be epileptogenic, if integrity of the blood-brain barrier is weakened (van Vliet, Aronica and Gorter, 2014). However IL-10 acts on tight junction proteins to reinforce the barrier (Lin et al, 2018). The functional consequences of such compensation via the upregulation of molecules with regenerative actions, potentially opposed to pro-inflammatory actions, in regions of neuronal loss remain to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Microglial phenotypes in the human epileptic temporal lobe

Morin‐Brureau

Milior

Royer

et al. 2018

Brain

View full text Add to dashboard Cite

Microglia, immune cells of the brain, are highly plastic and possess multiple functional phenotypes. Differences in phenotype in different regions and different states of epileptic human brain have been little studied. Here we use transcriptomics, anatomy, imaging of living cells and ELISA measurements of cytokine release to examine microglia from patients with temporal lobe epilepsies. Two distinct microglial phenotypes were explored. First we asked how microglial phenotype differs between regions of high and low neuronal loss in the same brain. Secondly we asked how microglial phenotype is changed by a recent seizure. In sclerotic areas with few neurons, microglia have an amoeboid rather than ramified shape, express activation markers and respond faster to purinergic stimuli. The repairing interleukin, IL-10, regulates the basal phenotype of microglia in the CA1 and CA3 regions with neuronal loss and gliosis. To understand changes in phenotype induced by a seizure, we estimated the delay from the last seizure until tissue collection from changes in reads for immediate early gene transcripts. Pseudotime ordering of this data was validated by comparison with results from kainate-treated mice. It revealed a local and transient phenotype in which microglia secrete the human interleukin CXCL8, IL-1B and other cytokines. This secretory response is mediated in part via the NRLP3 inflammasome.

show abstract

Section: Discussionmentioning

confidence: 99%

Microglial phenotypes in the human epileptic temporal lobe

Morin‐Brureau

Milior

Royer

et al. 2018

Brain

View full text Add to dashboard Cite

show abstract

“…The 7 most highly concentrated C/Cs (GRO KC, LIX, IP-10, MIP-2, MCP-1, RANTES, and IL-6) in Figure 1Bb were included in this group. LIX (Wang et al, 2016), GRO/KC (Maysami et al, 2015), IP-10 (Chai et al, 2015), MIP-2 (Shaftel et al, 2007), MCP-1 (Yao and Tsirka, 2014), RANTES (Ubogu et al, 2006), IL-6 (Paul et al, 2003), and IL-10 (Lin et al, 2018) play roles in BBB disruption during neuroinflammation. By immunostaining, we confirmed that the main resource of GRO KC was astrocytes, while only minor signals were detected in LPS-MG. Further experiments are necessary to clarify the contribution of astrocytes and activated microglia to the final concentration of each cytokine.…”

Section: Discussionmentioning

confidence: 99%

Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model

Shigemoto-Mogami

Hoshikawa

Sato

2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Severe neuroinflammation is associated with blood brain barrier (BBB) disruption in CNS diseases. Although microglial activation and the subsequent changes in cytokine/chemokine (C/C) concentrations are thought to be key steps in the development of neuroinflammation, little data are available concerning the interaction of microglia with BBB cells. In this study, we investigated this interaction by adding LPS-activated microglia (LPS-MG) to the abluminal side of a BBB model composed of endothelial cells (EC), pericytes (Peri) and astrocytes (Ast). We then examined the abluminal concentrations of 27 C/Cs and the interactions between the LPS-MG and BBB cells. LPS-MG caused collapse of the BBB, revealed by decreases in the trans-endothelial electrical resistance (TEER) and by changes in the expression levels of tight junction (TJ) proteins. Under these conditions, 19 C/Cs were markedly increased on the abluminal side. Unexpectedly, although LPS-MG alone released 10 of the 19 C/Cs, their concentrations were much lower than those detected on the abluminal side of the BBB model supplemented with LPS-MG. Co-culture of LPS-MG with Ast caused marked increases in 12 of the 19 C/Cs, while co-culture of LPS-MG with EC and Peri resulted in a significant increase in only 1 of the 19 C/Cs (fractalkine). These results suggest that C/C dynamics in this system are not only caused by activated microglia but also are due to the interaction between activated microglia and astrocytes.

show abstract

“…[31][32][33][34][35][36][37][38] In addition to modulating dendritic cell function, Tregs are known to suppress effector T cells (Teffs) through different mechanisms, including cytolysis, competition for metabolites, and release of soluble immunosuppressive cytokines such as IL-10. [39][40][41][42] However, the cytoprotective effects of Tregs or IL-10 on CEnCs have not been previously studied. [39][40][41][42] However, the cytoprotective effects of Tregs or IL-10 on CEnCs have not been previously studied.…”

Section: Introductionmentioning

confidence: 99%

“…18,38 Of note, there is evidence that IL-10 itself provides cytoprotection for hepatocytes, neurons, and brain microvascular endothelial cells. [39][40][41][42] However, the cytoprotective effects of Tregs or IL-10 on CEnCs have not been previously studied.…”

Section: Introductionmentioning

confidence: 99%

Regulatory T cells promote corneal endothelial cell survival following transplantation via interleukin-10

Coco

Foulsham

Yin

et al. 2020

American Journal of Transplantation

View full text Add to dashboard Cite

| INTRODUC TI ONCorneal transplantation is the most common form of tissue grafting worldwide. 1 When performed on an uninflamed and nonvascularized host bed, the graft survival rate exceeds 90%. 2 However, inflammation and vascularization of the host bed disrupt the cornea's relatively tolerant immune microenvironment, and graft survival rates fall to ≈50% despite maximum immunosuppression in highrisk recipients. 3-5 Immune rejection is the leading cause of corneal graft failure. 6 Corneal endothelial cells (CEnCs) are the target of the effector immune response mediated primarily by graft-targeting CD4 + interferon gamma (IFNγ + ) T helper type 1 (Th1) cells. 7,8 When the CEnC count decreases beyond a certain threshold, they are no longer capable of maintaining corneal graft transparency and the graft fails. 9,10 Substantial progress has been made in determining the mechanisms by which host factors, such as recipient bed vascularity and inflammation, influence the immune response to corneal allografts. 11-15 Forkhead box protein 3 (Foxp3)-positive regulatory T cells (Tregs) are a subset of CD4 + T cells that play a critical role in maintaining immune tolerance. 16 Studies performed by our laboratory 17-24 and others 25-27 indicate the critical contribution of Foxp3 + Tregs to immune tolerance in the setting of corneal transplantation.The functional competence of corneal endothelial cells (CEnCs) is critical for survival of corneal allografts, but these cells are often targets of the immune response mediated by graft-attacking effector T cells. Although regulatory T cells (Tregs) have been studied for their role in regulating the host's alloimmune response towards the graft, the cytoprotective function of these cells on CEnCs has not been investigated. The aim of this study was to determine whether Tregs suppress effector T cell-mediated and inflammatory cytokine-induced CEnC death, and to elucidate the mechanism by which this cytoprotection occurs. Using 2 well-established models of corneal transplantation (low-risk and high-risk models), we show that Tregs derived from low-risk graft recipients have a superior capacity in protecting CEnCs against effector T cellmediated and interferon-γ and tumor necrosis factor-α-induced cell death compared to Tregs derived from high-risk hosts. We further demonstrate that the cytoprotective function of Tregs derived from low-risk hosts occurs independently of direct cell-cell contact and is mediated by the immunoregulatory cytokine IL-10. Our study is the first to report that Tregs provide cytoprotection for CEnCs through secretion of IL-10, indicating potentially novel therapeutic targets for enhancing CEnC survival following corneal transplantation. K E Y W O R D Sanimal models: murine, basic (laboratory) research/science, corneal transplantation/ ophthalmology, immune regulation, T cell biology, tolerance

show abstract

Interleukin-10 attenuates impairment of the blood-brain barrier in a severe acute pancreatitis rat model

Cited by 44 publications

References 41 publications

Microglial phenotypes in the human epileptic temporal lobe

Microglial phenotypes in the human epileptic temporal lobe

Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model

Regulatory T cells promote corneal endothelial cell survival following transplantation via interleukin-10

Contact Info

Product

Resources

About