Roles of inflammation response in microglia cell through Toll-like receptors 2/interleukin-23/interleukin-17 pathway in cerebral ischemia/reperfusion injury

Lv, Mei; Liu, Y.; Zhang, J.; Sun, Lijie; Liu, Z.; Zhang, S.; Wang, Bo; Su, Dan; Su, Zhi

doi:10.1016/j.neuroscience.2010.11.066

Cited by 90 publications

(57 citation statements)

References 60 publications

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“…The CysLT 2 R antagonist HAMI 3379 inhibits microglial activation, which indirectly attenuates ischemic neuronal injury, whereas the CysLT 1 R antagonist montelukast inhibits ischemic neuronal injury in receptordependent and -independent manners. inflammatory cytokines, reactive oxygen species, and proteinases (Dheen et al, 2007;Lv et al, 2011;Zhang et al, 2012). Our results revealed that CysLT-activated microglia mediated ischemic neuronal injury in our experimental conditions, and this might have resulted from releasing harmful cytokines, such as IL-1b and TNF-a (Amantea et al, 2010;Lambertsen et al, 2012).…”

Section: Discussionmentioning

confidence: 53%

HAMI 3379, a CysLT₂ Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation

Zhang

Wang

et al. 2013

J Pharmacol Exp Ther

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The cysteinyl leukotrienes (CysLTs) are inflammatory mediators closely associated with neuronal injury after brain ischemia through the activation of their receptors, CysLT1R and CysLT2R. Here we investigated the involvement of both receptors in oxygen-glucose deprivation/recovery (OGD/R)-induced ischemic neuronal injury and the effect of the novel CysLT2R antagonistin comparison with the CysLT1R antagonist montelukast. In primary neurons, neither the nonselective agonist leukotriene D4 (LTD4) nor the CysLT2R agonist N-methyl-leukotriene C4 (NMLTC4) induced neuronal injury, and HAMI 3379 did not affect OGD/R-induced neuronal injury. However, in addition to OGD/R, LTD4 and NMLTC4 induced cell injury and neuronal loss in mixed cultures of cortical cells, and neuronal loss and necrosis in neuron-microglial cocultures. Moreover, they induced phagocytosis and cytokine release (interleukin-1b and tumor necrosis factor-a) from primary microglia, and conditioned medium from the treated microglia induced neuronal necrosis. HAMI 3379 inhibited all of these responses, and its effects were the same as those of CysLT2R interference by CysLT2R short hairpin RNA, indicating CysLT2R dependence. In comparison, montelukast moderately inhibited OGD/R-induced primary neuronal injury and most OGD/R-and LTD4-induced (but not NMLTC4-induced) responses in mixed cultures, cocultures, and microglia. The effects of montelukast were both dependent and independent of CysLT1Rs because interference by CysLT1R small interfering RNA had limited effects on neuronal injury in neuron-microglial cocultures and on cytokine release from microglia. Our findings indicated that HAMI 3379 effectively blocked CysLT2R-mediated microglial activation, thereby indirectly attenuating ischemic neuronal injury. Therefore, CysLT2R antagonists may represent a new type of therapeutic agent in the treatment of ischemic stroke.

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Section: Discussionmentioning

confidence: 53%

HAMI 3379, a CysLT₂ Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation

Zhang

Wang

et al. 2013

J Pharmacol Exp Ther

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“…This molecule has been shown to induce IL-23 expression from macrophages by activating TLR2 and TLR4, which in response induce the expression of IL-17 by immune cells [75]. These findings are supported by the fact that exogenous IL-17 is able to directly increase cerebral ischemia-induced neuronal damage, indicating that the activation of the TLR2/IL-23/IL-17 axis in microglia might be partially responsible for inducing neuronal damage after cerebral ischemia reperfusion [59]. Moreover, there may be an important interaction between antigen-presenting cells (APCs), including microglia as well as infiltrating monocytes/macrophages, and T cells via IL-23, which further stimulates the differentiation of IL-17-producing cells infiltrating the brain.…”

Section: Il-17 In Ischemic Brain Injurymentioning

confidence: 83%

The role of IL-17 in CNS diseases

2015

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Cytokines of the IL-17 family are uniquely placed on the border between immune cells and tissue. Although IL-17 was originally found to induce the activation and mobilization of neutrophils to sites of inflammation, its tissue-specific function is not yet fully understood. The best-studied IL-17 family members, IL-17A and IL-17F, are both typically produced by immune cells such as Th17, γδ T cells and innate lymphoid cells group 3. However, the cells that respond to these cytokines are mostly found in inflamed tissue. As seen in psoriatic skin lesions or in joints of rheumatoid arthritis patients, high levels of IL-17 have been detected in the central nervous system (CNS) during inflammatory responses. Here, we provide a general review of the molecular function of IL-17 and its role in the CNS in particular. Of the different inflammatory conditions of the CNS, we found multiple sclerosis (MS) to be the one most associated with the presence of Th17 cells and IL-17. In particular, many studies using the murine model for MS, experimental autoimmune encephalomyelitis, found a clear association of Th17 and IL-17 with disease severity and progression. We summarize the recent advances made in correlating the presence of IL-17 with impaired blood-brain barrier integrity as well as the activation of astrocytes and microglia and the consequences for disease progression. There is also evidence that IL-17 plays a pathogenic role in the post-ischemic phase of stroke as well as its experimental model. We review the limited but promising data on the sources of post-stroke IL-17 production and its effects on CNS-resident target cells. In addition to MS and stroke, there is also evidence linking high levels of IL-17 to depression, as a frequent comorbidity of several inflammatory diseases, as well as to different types of infections of the CNS. The evidence we supply here suggests that inhibiting the function of the IL-17 cytokine family could have a beneficial effect on pathogenic conditions in the CNS.

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“…5), and those that were present were situated in contact with blood vessels (Fig. 5A) (Greter et al, 2005;Lv et al, 2011;Prodinger et al, 2011;Puntener et al, 2012). Further combined analysis by FC and IF with an array of different cellular markers will shed new light on the phenotype, activation stage and role of brain myeloid cells in the response to diverse neuroinflammatory stimuli.…”

Section: Discussionmentioning

confidence: 99%

DNGR-1⁺dendritic cells are located in meningeal membrane and choroid plexus of the noninjured brain

Quintana

Fernández

Velasco

et al. 2015

Glia

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The role and different origin of brain myeloid cells in the brain is central to understanding how the central nervous system (CNS) responds to injury. C-type lectin receptor family 9, member A (DNGR-1/CLEC9A) is a marker of specific DC subsets that share functional similarities, such as CD8α(+) DCs in lymphoid tissues and CD103(+) CD11b(low) DCs in peripheral tissues. Here, we analyzed the presence of DNGR-1 in DCs present in the mouse brain (bDCs). Dngr-1/Clec9a mRNA is expressed mainly in the meningeal membranes and choroid plexus (m/Ch), and its expression is enhanced by fms-like tyrosine kinase 3 ligand (Flt3L), a cytokine involved in DC homeostasis. Using Clec9a(egfp/egfp) mice, we show that Flt3L induces accumulation of DNGR-1-EGFP(+) cells in the brain m/Ch. Most of these cells also express major histocompatibility complex class II (MHCII) molecules. We also observed an increase in specific markers of cDC CD8α+ cells such as Batf-3 and Irf-8, but not of costimulatory molecules such as Cd80 and Cd86, indicating an immature phenotype for these bDCs in the noninjured brain. The presence of DNGR-1 in the brain provides a potential marker for the study of this specific brain cell subset. Knowledge and targeting of brain antigen presenting cells (APCs) has implications for the fight against brain diseases such as neuroinflammation-based neurodegenerative diseases, microbe-induced encephalitis, and brain tumors such as gliomas.

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Roles of inflammation response in microglia cell through Toll-like receptors 2/interleukin-23/interleukin-17 pathway in cerebral ischemia/reperfusion injury

Cited by 90 publications

References 60 publications

HAMI 3379, a CysLT₂ Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation

HAMI 3379, a CysLT₂ Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation

The role of IL-17 in CNS diseases

DNGR-1⁺dendritic cells are located in meningeal membrane and choroid plexus of the noninjured brain

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Roles of inflammation response in microglia cell through Toll-like receptors 2/interleukin-23/interleukin-17 pathway in cerebral ischemia/reperfusion injury

Cited by 90 publications

References 60 publications

HAMI 3379, a CysLT2 Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation

HAMI 3379, a CysLT2 Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation

The role of IL-17 in CNS diseases

DNGR-1+dendritic cells are located in meningeal membrane and choroid plexus of the noninjured brain

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HAMI 3379, a CysLT₂ Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation

HAMI 3379, a CysLT₂ Receptor Antagonist, Attenuates Ischemia-Like Neuronal Injury by Inhibiting Microglial Activation

DNGR-1⁺dendritic cells are located in meningeal membrane and choroid plexus of the noninjured brain