期刊
JOURNAL OF IMMUNOLOGY
卷 166, 期 4, 页码 2695-2704出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.166.4.2695
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- NIMH NIH HHS [MH55795] Funding Source: Medline
- NINDS NIH HHS [NS29719, NS34856 , +] Funding Source: Medline
Chemokines constitute a superfamily of proteins that function as chemoattractants and activators of leukocytes, Astrocytes, the major glial cell type in the CNS, are a source of chemokines within the diseased brain. Specifically, we have shown that primary human astrocytes and human astroglioma cell lines produce the CXC chemokines IFN-gamma -inducible protein-10 and IL-8 and the CC chemokines monocyte chemoattractant protein-1 and RANTES in response to stimuli such as TNF-alpha, IL-1 beta, and IFN-gamma. In this study, we investigated chemokine receptor expression and function on human astroglioma cells. Enhancement of CXC chemokine receptor 4 (CXCR4) mRNA expression was observed upon treatment with the cytokines TNF-alpha and IL-1 beta. The peak of CXCR4 expression in response to TNF-alpha and IL-1 beta was 8 and 4 h, respectively. CXCR4 protein expression was also enhanced upon treatment with TNF-alpha and IL-1 beta (2- to 3-fold). To study the functional relevance of CXCR4 expression, stable astroglioma transfectants expressing high levels of CXCR4 were generated. Stimulation of cells with the ligand for CXCR4, stromal cell-derived factor-la (SDF-1 alpha), resulted in an elevation in intracellular Ca2+ concentration and activation of the mitogen-activated protein kinase cascade, specifically, extracellular signal-regulated kinase 2 (ERK2) mitogen-activated protein kinase, Of most interest, SDF-1 alpha treatment induced expression of the chemokines monocyte chemoattractant protein-1, IL-8, and IFN-gamma -inducible protein-10. SDF-1 alpha -induced chemokine expression was abrogated upon inclusion of U0126, a pharmacological inhibitor of ERK1/2, indicating that the ERK signaling cascade is involved in this response. Collectively, these data suggest that CXCR4-mediated signaling pathways in astroglioma cells may be another mechanism for these cells to express chemokines involved in angiogenesis and inflammation,
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