Production of macrophage inflammatory protein-2 following hypoxia/reoxygenation in glial cells

Wang, Ju Yu; Shum, Andrew Y C; Chao, Chun C.; Kuo, Jon Son; Wang, Jia Yi

doi:10.1002/1098-1136(200011)32:2<155::aid-glia50>3.0.co;2-4

Cited by 35 publications

(14 citation statements)

References 42 publications

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“…Cat C has been proved to take part in the release of chemokines, and Cat C gene could deficiency decreases the release of CXCL2 in the peripheral circulation (Pagano et al, 2007). Because CXCL2 is produced by leukocytes (Gu et al, 1999) in the circulatory system, and by microglia/macrophages (Wang et al, 2000; Rouault et al, 2013) and astrocytes (Wang et al, 2014) in the CNS, we were curious about the level of CXCL2 expression in wild and Cys F KO mice after cuprizone treatment. Therefore, real-time quantitative PCR and ELISA were preformed to detect the expression of CXCL2 mRNA and protein, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…In the present study, we found a significantly increased number of microglia/macrophages accumulated in demyelinated areas in Cys F KO mice, which may be associated with chemoattraction mediated by CXCL2. CXCL2, a member of the CXC chemokine family, also called macrophage inflammatory protein 2-alpha (MIP2-alpha), is produced not only by leukocytes (Gu et al, 1999) in the circulatory system, but also by microglia/macrophages (Wang et al, 2000; Rouault et al, 2013) and astrocytes (Wang et al, 2014) in the CNS. CXCL2 mobilizes cells by interacting with a cell surface chemokine receptor (CXCR2), whose expression has been identified on many types of resident cells in the CNS, including neurons and glial cells (Goczalik et al, 2008), and leukocytes, including neutrophils, monocytes, and T cells in the peripheral system (Liu Y. et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model

Liang

Zhang

et al. 2016

Front. Mol. Neurosci.

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Although the precise mechanism underlying initial lesion development in multiple sclerosis (MS) remains unclear, CNS inflammation has long been associated with demyelination, and axonal degeneration. The activation of microglia/macrophages, which serve as innate immune cells in the CNS, is the first reaction to even minor pathologic changes in the CNS and is considered an initial pathogenic event in MS. Microglial activation accompanies a variety of gene expressions, including cystatin F (Cys F), which belongs to the cystatin superfamily and is one of the cathepsin inhibitors. In our previous study we showed that Cys F has a unique expression pattern in microglia/macrophages in the demyelination process. Specifically, the timing of Cys F induction correlated with ongoing demyelination, and the sites of Cys F expression overlapped with areas of remyelination. Cys F induction ceased in chronic demyelination when remyelination capacity was lost, suggesting that Cys F expressed by microglia/macrophages may play an important role in demyelination and/or remyelination. The functional role of Cys F in demyelinating disease of the CNS, however, is unclear. Cys F gene knockout mice were used in the current study to clarify the functional role of Cys F in the demyelination process in a cuprizone-induced demyelination animal model. We demonstrated that absence of the Cys F gene and the resulting disinhibition of cathepsin C (Cat C) aggravates the demyelination, and this finding may be related to the increased expression of the glia-derived chemokine, CXCL2, which may attract inflammatory cells to sites of myelin sheath damage. This effect was reversed by knock down of the Cat C gene. The findings gain further insight to function of Cat C in pathophysiology of MS, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model

Liang

Zhang

et al. 2016

Front. Mol. Neurosci.

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“…Generally in the adult CNS, chemokines are involved in modulation of neurotransmission, neuron-glial interaction and prevention of neurotoxicity (Miller et al, 2008). The chemokine CXCL12 (SDF-1α), a ligand for CXCR4 and CXCR7, is constitutively expressed by neurons and astrocytes, but the macrophage inflammatory peptide-2 (MIP-2) ligand for CXCR2 is produced by microglia in response to toxic stimuli such as Aβ peptides (Wang et al, 2000; Ito et al, 2006). Cortical regions of the brain and the hippocampus express the chemokine receptors CXCR2, CXCR4, CX 3 CR1 (Horuk et al, 1997; Lavi et al, 1997; Meucci et al, 1998; Xia and Hyman, 1999; Meucci et al, 2000; Wang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1α, suppress amyloid β-induced neurotoxicity

Raman

Milatovic

Milatović

et al. 2011

Toxicology and Applied Pharmacology

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Alzheimer’s disease (AD) is characterized by a progressive cognitive decline and accumulation of neurotoxic oligomeric peptides amyloid-β (Aβ). Although the molecular events are not entirely known, it has become evident that inflammation, environmental and other risk factors may play a causal, disruptive and/or protective role in the development of AD. The present study investigated the ability of the chemokines, macrophage inflammatory protein-2 (MIP-2) and stromal cell-derived factor-1α (SDF-1α), the respective ligands for chemokine receptors CXCR2 and CXCR4, to suppress Aβ-induced neurotoxicity in vitro and in vivo. Pretreatment with MIP-2 or SDF-1α significantly protected neurons from Aβ-induced dendritic regression and apoptosis in vitro through activation of Akt, ERK1/2 and maintenance of metalloproteinase ADAM17 especially with SDF-1α. Intra-cerebroventricular (ICV) injection of Aβ led to reduction in dendritic length and spine density of pyramidal neurons in the CA1 area of the hippocampus and increased oxidative damage 24 h following the exposure. The Aβ-induced morphometric changes of neurons and increase in biomarkers of oxidative damage, F2-isoprostanes, was significantly inhibited by pretreatment with the chemokines MIP-2 or SDF-1α. Additionally, MIP-2 or SDF-1α was able to suppress the aberrant mislocalization of p21-activated kinase (PAK), one of the proteins involved in the maintenance of dendritic spines. Furthermore, MIP-2 also protected neurons against Aβ neurotoxicity in CXCR2−/− mice, potentially through observed up regulation of CXCR1 mRNA. Understanding the neuroprotective potential of chemokines is crucial in defining the role for their employment during the early stages of neurodegeneration.

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“…These cells begin to proliferate, migrate and differentiate, release cytotoxins and inflammatory mediators, secrete cytokines, and upregulate immune expression. A series of previous studies showed that activated microglia in vitro released a large number of free radicals and inflammatory cytokines, which activated or aggravated neuronal damage; conversely, neuronal damage activated microglial cells, thus leading to a pathological cascade and aggravating the damage induced by ischemia[313233343536373839]. …”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 attenuates activated microglia-induced neuronal damage

Guo

et al. 2014

Neural Regen Res

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The microglia-mediated inflammatory reaction promotes neuronal damage under cerebral ischemia/hypoxia conditions. We therefore speculated that inhibition of hypoxia-induced microglial activation may alleviate neuronal damage. To test this hypothesis, we co-cultured ginsenoside Rb1, an active component of ginseng, and cortical neurons. Ginsenoside Rb1 protected neuronal morphology and structure in a single hypoxic culture system and in a hypoxic co-culture system with microglia, and reduced neuronal apoptosis and caspase-3 production. The protective effect was observable prior to placing in co-culture. Additionally, ginsenoside Rb1 inhibited levels of tumor necrosis factor-α in a co-culture system containing activated N9 microglial cells. Ginsenoside Rb1 also significantly decreased nitric oxide and superoxide production induced by N9 microglia. Our findings indicate that ginsenoside Rb1 attenuates damage to cerebral cortex neurons by downregulation of nitric oxide, superoxide, and tumor necrosis factor-α expression in hypoxia-activated microglia.

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Production of macrophage inflammatory protein-2 following hypoxia/reoxygenation in glial cells

Cited by 35 publications

References 42 publications

Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model

Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model

Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1α, suppress amyloid β-induced neurotoxicity

Ginsenoside Rb1 attenuates activated microglia-induced neuronal damage

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