Extracellular presence of IL-8 in the astrocyte-rich cultured cerebellar granule cells under acidosis

Watanabe, Yasuo; Miura, Izumi; Ohgami, Yusuke; Fujiwara, Michihiro

doi:10.1016/s0024-3205(98)00365-8

Cited by 16 publications

(12 citation statements)

References 21 publications

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“…Although the presence of a minor population of microglia cannot be completely excluded in the primary cultures of astrocytes, GRO/CINC‐1 secretion is unlikely to be because of the microglia upon PAR activation. This notion is proven by some previous reports (Watanabe et al. 1998; Hanisch et al.…”

Section: Resultssupporting

confidence: 73%

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The role of calcium in protease‐activated receptor‐induced secretion of chemokine GRO/CINC‐1 in rat brain astrocytes

Wang

Luo

Reiser

2007

Journal of Neurochemistry

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Our recent data showed that activation of protease-activated receptor (PAR)-1 and PAR-2 in rat astrocytes not only evokes calcium signaling, but also regulates the release of the chemokine growth-regulated oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1), a counterpart of the human GRO. This chemokine provides a feedback to protect astrocytes from toxic insults. Activated PAR-1 and PAR-2 were strong stimuli to induce the release of GRO/ CINC-1. The effect was comparable to that induced by TNF-a. However, the role of calcium in the PAR-induced GRO/CINC-1 secretion remains unknown. Here, we found that the pharmacological blockade of either calcium release from the intracellular stores, or influx from the extracellular space, increased PAR-1-and PAR-2-induced GRO/CINC-1 secretion. Under calcium-free conditions, the basal mRNA level of GRO/CINC-1 was clearly increased. Further studies revealed that the intracellular GRO/CINC-1 protein level was slightly increased by treatment with thrombin or TRag in calcium-free conditions. However, the amount of protein synthesized was largely reduced in the absence of extracellular calcium as compared to that under normal calcium conditions. Importantly, we found that the intracellularly formed GRO/CINC-1 was not secreted into the cell culture supernatant under calcium-free conditions. These data suggest a dual role of calcium. On the one side, an increase in cytosolic calcium negatively regulates PAR-induced GRO/CINC-1 gene expression in rat astrocytes, but on the other side, the basal level of calcium is the pre-requisite for GRO/CINC-1 protein synthesis and secretion.

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Section: Resultssupporting

confidence: 73%

“…The time course and the amounts of GRO/CINC‐1 released are highly consistent with acidosis‐induced rat IL‐8 (GRO/CINC‐1) secretion in astrocyte‐enriched cultures from cerebellum [see Fig. 1 in Watanabe et al. (1998)].…”

Section: Resultsmentioning

confidence: 57%

The role of calcium in protease‐activated receptor‐induced secretion of chemokine GRO/CINC‐1 in rat brain astrocytes

Wang

Luo

Reiser

2007

Journal of Neurochemistry

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“…IL-8 release into the CSF after brain injury is associated with blood-brain barrier dysfunction (6) and nerve growth factor production (34). IL-8 is produced by astrocytes under acidosis (66), by blood mononuclear cells after ischemic stroke (35), and in neoplastic and infectious diseases of the human CNS (35). Also, a recent publication suggests that IL-8 contributes to shear flow-resistant adhesion of macrophages to vascular endothelial cells (20).…”

Section: Discussionmentioning

confidence: 99%

Induction of the Chemokines Interleukin-8 and IP-10 by Human Immunodeficiency Virus Type 1 Tat in Astrocytes

Kutsch

Nath

et al. 2000

J Virol

165

118

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A finding commonly observed in human immunodeficiency virus type 1 (HIV-1)-infected patients is invasion of the brain by activated T cells and infected macrophages, eventually leading to the development of neurological disorders and HIV-1-associated dementia. The recruitment of T cells and macrophages into the brain is likely the result of chemokine expression. Indeed, earlier studies revealed that levels of different chemokines were increased in the cerebrospinal fluid of HIV-1-infected patients whereas possible triggers and cellular sources for chemokine expression in the brain remain widely undefined. As previous studies indicated that HIV-1 Tat, the retroviral transactivator, is capable of inducing a variety of cellular genes, we investigated its capacity to induce production of chemokines in astrocytes. Herein, we demonstrate that HIV-1 Tat 72aa is a potent inducer of MCP-1, interleukin-8 (IL-8), and IP-10 expression in astrocytes. Levels of induced IP-10 protein were sufficiently high to induce chemotaxis of peripheral blood lymphocytes. In addition, Tat 72aa induced IL-8 expression in astrocytes. IL-8 mRNA induction was seen less then 1 h after Tat 72aa stimulation, and levels remained elevated for up to 24 h, leading to IL-8 protein production. Tat 72aa -mediated MCP-1 and IL-8 mRNA induction was susceptible to inhibition by the MEK1/2 inhibitor UO126 but was only modestly decreased by the inclusion of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190. In contrast, Tat-mediated IP-10 mRNA induction was suppressed by SB202190 but not by the MEK1/2 inhibitor UO126. These findings indicate that MAPKs play a major role in Tat 72aa -mediated chemokine induction in astrocytes.

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“…We have also recently identi®ed two NF-kB binding sites on the VEGF 3'-UTR, 5'-AGGAGCCTC-3' (+15 to +23) and 5'-GGGGATTCCC-3' (+1171 to +1180). It is known that acidic pH activates both AP-1 and NFkB, which are important to the upregulation of IL-8 by acidosis (Watanabe et al, 1998;Shi et al, 1999Shi et al, , 2000Xie, 2001). Bellocq et al (1998) have also shown that these factors are involved in extracellular pH-mediated upregulation of inducible nitric oxide synthase.…”

mentioning

confidence: 99%

Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells

et al. 2001

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Extracellular presence of IL-8 in the astrocyte-rich cultured cerebellar granule cells under acidosis

Cited by 16 publications

References 21 publications

The role of calcium in protease‐activated receptor‐induced secretion of chemokine GRO/CINC‐1 in rat brain astrocytes

The role of calcium in protease‐activated receptor‐induced secretion of chemokine GRO/CINC‐1 in rat brain astrocytes

Induction of the Chemokines Interleukin-8 and IP-10 by Human Immunodeficiency Virus Type 1 Tat in Astrocytes

Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells

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