scholarly journals Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke

Blood ◽  
2012 ◽  
Vol 120 (18) ◽  
pp. 3793-3802 ◽  
Author(s):  
Mathias Gelderblom ◽  
Anna Weymar ◽  
Christian Bernreuther ◽  
Joachim Velden ◽  
Priyadharshini Arunachalam ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Murine Model ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Option ◽  
Ischemia Reperfusion ◽  
Γδ T Cells ◽  
Tnf Α ◽  
Selective Targeting ◽  
Enhanced Secretion

Abstract The devastating effect of ischemic stroke is attenuated in mice lacking conventional and unconventional T cells, suggesting that inflammation enhances tissue damage in cerebral ischemia. We explored the functional role of αβ and γδ T cells in a murine model of stroke and distinguished 2 different T cell–dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-γ produced by CD4+ T cells induced TNF-α production in macrophages, whereas IL-17A secreted by γδ T cells led to neutrophil recruitment. The synergistic effect of TNF-α and IL-17A on astrocytes resulted in enhanced secretion of CXCL-1, a neutrophil chemoattractant. Application of an IL-17A–blocking antibody within 3 hours after stroke induction decreased infarct size and improved neurologic outcome in the murine model. In autoptic brain tissue of patients who had a stroke, we detected IL-17A–positive lymphocytes, suggesting that this aspect of the inflammatory cascade is also relevant in the human brain. We propose that selective targeting of IL-17A signaling might provide a new therapeutic option for the treatment of stroke.

scholarly journals CD4 T cells promote tissue inflammation via CD40 signaling without de novo activation in a murine model of liver ischemia/reperfusion injury

Hepatology ◽  
2009 ◽  
Vol 50 (5) ◽  
pp. 1537-1546 ◽  
Author(s):  
Xiuda Shen ◽  
Yue Wang ◽  
Feng Gao ◽  
Feng Ren ◽  
Ronald W. Busuttil ◽  
...  
Keyword(s):  
T Cells ◽  
Reperfusion Injury ◽  
Murine Model ◽  
Cd4 T Cells ◽  
De Novo ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Ischemia ◽  
Tissue Inflammation

scholarly journals INCREASED TRAFFICKING OF MESENTERIC LYMPH-DERIVED γδ T CELLS INTO INTESTINAL MUCOSA IS ASSOCIATED WITH GUT INJURY AFTER INTESTINAL ISCHEMIA-REPERFUSION IN RATS

Lymphology ◽  
2019 ◽  
Vol 52 (2) ◽  
Author(s):  
J Yang ◽  
Y Shen ◽  
RQ Wu ◽  
H Zhu ◽  
Y Jin ◽  
...  
Keyword(s):  
T Cells ◽  
Intestinal Mucosa ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Γδ T Cells ◽  
Intestinal Injury ◽  
Endotoxin Concentration ◽  
Mesenteric Lymph ◽  
Tnf Α ◽  
Intestinal Ischemia Reperfusion

We sought to investigate the effects of mesenteric lymph-derived γδ T cells trafficking into intestinal mucosa on gut injury after intestinal ischemia-reperfusion (IIR). γδ T cells were separated from mesenteric lymph and then infused into the femoral vein of rats after the γδ T cells were labeled with 51Cr. Migration of γδ T cells in vivo across the intestinal mucosa was determined by γ-counter. Meanwhile, TNF-α activity and endotoxin concentration in mesenteric lymph were detected. The population of γδ T cells of Peyer's patches in the small intestines was analyzed by immunofluorescence double staining methods and flow cytometry. After IIR injury, the mean optical density value (MOD) and population of γδ T cells in Peyer's patches of the gut and migration of 51Cr-γδ T cells across the intestinal mucosa were significantly increased, which had highly positive correlations to degree of intestinal injury, TNF-α levels and endotoxin concentration in mesenteric lymph after reperfusion. The increased population of γδ T cells derived from mesenteric lymph trafficking into the intestinal mucosa might promote the small intestinal injury after IIR.

scholarly journals Pelargonidin ameliorates MCAO-induced cerebral ischemia/reperfusion injury in rats by the action on the Nrf2/HO-1 pathway

2021 ◽  
Vol 12 (1) ◽  
pp. 020-031
Author(s):  
Kong Fu ◽  
Miancong Chen ◽  
Hua Zheng ◽  
Chuanzi Li ◽  
Fan Yang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
Learning Ability ◽  
Morris Water Maze Test ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury

Abstract Background Morbidity and mortality remain high for ischemic stroke victims, and at present these patients lack effective neuroprotective agents, which improve the cure rate. In recent years, studies have shown that pelargonidin has many biological actions. However, few studies are available regarding the pelargonidin treatment of cerebral ischemia. Methods The rat middle cerebral artery occlusion (MCAO) model was established to investigate the neuroprotective effect of pelargonidin on cerebral ischemia/reperfusion injury. Reperfusion was performed 2 h after ischemia; magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining were used to measure the volume of cerebral ischemia. Both modified neurological severity scores (mNSSs) and Morris water maze test were used to assess the neurological functions. ELISA was applied to determine the levels of TNF-α, TGF-β, IL-6, IL-10, MDA, and SOD. The expression of Nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein in brain tissue was measured by immunofluorescence and Western blot assays. Results The results showed that pelargonidin could effectively reduce the volume of cerebral ischemia and improve the neurological function in MCAO rats, thereby improving memory and learning ability. With the corresponding decreases in the expression of TNF-α, TGF-β, IL-6, and MDA, the level of IL-10 and SOD increased and also promoted the nuclear metastasis of Nrf2 and the expression of HO-1 in ischemic brain tissues. Conclusions Our data demonstrated that pelargonidin ameliorated neurological function deficits in MCAO rats, and its potential mechanism of action was associated with overexpression of the Nrf2/HO-1-signaling pathway. This study will provide a new approach to treat cerebral ischemia/reperfusion injury.

scholarly journals Murine Model of Intestinal Ischemia-reperfusion Injury

10.3791/53881 ◽  
2016 ◽  
Author(s):  
Ekaterina O. Gubernatorova ◽  
Ernesto Perez-Chanona ◽  
Ekaterina P. Koroleva ◽  
Christian Jobin ◽  
Alexei V. Tumanov
Keyword(s):  
Reperfusion Injury ◽  
Murine Model ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Intestinal Ischemia Reperfusion

Flaxseed Protects Against the Inflammatory Phase of Lung Ischemia Reperfusion Injury in a Murine Model

2010 ◽  
Vol 158 (2) ◽  
pp. 358
Author(s):  
S.S. Razi ◽  
G. Schwartz ◽  
D. Boone ◽  
X. Li ◽  
S. Belsley ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Murine Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inflammatory Phase

scholarly journals Distinct contributions of CD4+ T cell subsets in hepatic ischemia/reperfusion injury

2009 ◽  
Vol 296 (5) ◽  
pp. G1054-G1059 ◽  
Author(s):  
Satoshi Kuboki ◽  
Nozomu Sakai ◽  
Johannes Tschöp ◽  
Michael J. Edwards ◽  
Alex B. Lentsch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Ischemia Reperfusion ◽  
Γδ T Cells ◽  
Nkt Cells ◽  
T Cell Subsets ◽  
Wild Type ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Helper T cells are known to mediate hepatic ischemia/reperfusion (I/R) injury. However, the precise mechanisms and subsets of CD4+ T cells that contribute to this injury are still controversial. Therefore, we sought to determine the contributions of different CD4+ T cell subsets during hepatic I/R injury. Wild-type, OT-II, or T cell receptor (TCR)-δ-deficient mice were subjected to 90 min of partial hepatic ischemia followed by 8 h of reperfusion. Additionally, wild-type mice were pretreated with anti-CD1d, -NK1.1, or -IL-2R-α antibodies before I/R injury. OT-II mice had diminished liver injury compared with wild-type mice, implicating that antigen-dependent activation of CD4+ T cells through TCRs is involved in hepatic I/R injury. TCR-δ knockout mice had decreased hepatic neutrophil accumulation, suggesting that γδ T cells regulate neutrophil recruitment. We found that natural killer T (NKT) cells, but not NK cells, contribute to hepatic I/R injury via CD1d-dependent activation of their TCRs, as depletion of NKT cells by anti-CD1d antibody or depletion of both NKT cells and NK cells by anti-NK1.1 attenuated liver injury. Although regulatory T cells (Treg) are known to suppress T cell-dependent inflammation, depletion of Treg cells had little effect on hepatic I/R injury. The data suggest that antigen-dependent activation of CD4+ T cells contributes to hepatic I/R injury. Among the subsets of CD4+ T cells, it appears that γδ T cells contribute to neutrophil recruitment and that NKT cells directly injure the liver. In contrast, NK cells and Treg have little effects on hepatic I/R injury.

Abstract P332: Role of T-Lymphocytes in the Long-Term Blood Pressure and Renal Disease Effects of Acute Renal Ischemia-Reperfusion Injury

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Bernardo Lopez ◽  
Galina Petrova ◽  
Justine M Abais-Battad ◽  
Hayley Lund ◽  
Daniel Fehrenbach ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Renal Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Immunosuppressive Agents ◽  
High Salt ◽  
Renal Ischemia ◽  
Salt Sensitive Hypertension

Epidemiological data indicates that acute kidney injury (AKI) is an independent risk factor for the development of hypertension and chronic kidney disease in patients. Previous studies demonstrated that rats develop sodium-dependent hypertension and kidney damage following experimental AKI induced by a renal ischemia-reperfusion (IR) insult; furthermore, these high salt deleterious effects could be blunted by administration of immunosuppressive agents. The present study was performed on Dahl SS (SS) rats and SS rats with a null mutation in the CD247 gene (SS-CD247) leading to depletion of T-lymphocytes in order to specifically examine the role of T cells in this response (n=5-6 rats/group). As assessed by serum creatinine (SCr) levels, no difference was observed in the initial response to IR injury between SS and SS-CD247: SCr increased from 0.44±0.03 to 2.16±0.32 mg/dl in SS rats 24 hours after an initial 30 minute period of renal ischemia and returned to control levels after 8 days of recovery. Moreover, no differences were noted in mean arterial pressure (MAP) or albumin excretion rate (UAlb) between SS and SS-CD247 after 43 days of recovery from IR injury while the rats were maintained on a low salt (0.4% NaCl) diet. When the rats were fed a 4.0% NaCl diet for two weeks, MAP and UAlb significantly increased in the sham SS to 178±9 mmHg and 189±25 mg/day, respectively; values significantly greater than observed in the sham SS-CD247 rats (148±2 mmHg and 87±17 mg/day). As expected, the SS rats recovered from IR injury demonstrated an exaggerated increase in MAP (peaking at 183±2 mmHg) and UAlb (275±54 mg/day) in response to high salt. There was no difference in the number of total CD3+ lymphocytes in the kidneys of IR and sham SS after high salt, though the ratio of CD4+/CD8+ T cells was increased in the IR group. Compared to sham CD247, an exaggerated elevation of MAP (157±9 mmHg) and UAlb (210±32 mg/day) was also observed in the SS-CD247 rats recovered from IR injury, demonstrating enhanced responsiveness following IR injury in animals lacking T cells. These data indicate that T lymphocytes amplify salt-sensitive hypertension and renal damage, but other mechanisms also mediate the salt-sensitive hypertension and renal damage that occurs in animals recovered from IR injury.

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