European journal of pharmacology, 2009-06, Vol.613 (1), p.146-154
2009
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- Autor(en) / Beteiligte
- Titel
- SDF-1alpha up-regulates interleukin-6 through CXCR4, PI3K/Akt, ERK, and NF-kappaB-dependent pathway in microglia
- Ist Teil von
- European journal of pharmacology, 2009-06, Vol.613 (1), p.146-154
- Ort / Verlag
- Netherlands: Elsevier B.V
- Erscheinungsjahr
- 2009
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- Stromal cell-derived factor-1 (SDF-1), also known as CXCL12, and its receptor CXC chemokine receptor 4 (CXCR4) express in various kinds of cells in central nervous system. The SDF-1/CXCR4 signaling pathway is regulated by diverse biological effects. SDF-1 is up-regulated in the ischemic penumbra following stroke and has been known to be associated with the homing of bone marrow cells to injury. However, the effect of SDF-1α/CXCR4 on cytokine production in microglia is mostly unknown. Here, we demonstrated that SDF-1α enhanced IL-6 production in both primary cultured microglia and BV-2 microglia. We further investigated the signaling pathway involved in IL-6 production stimulated by SDF-1α in microglia. SDF-1α increased IL-6 production in both protein and mRNA levels. These effects were attenuated by ERK, phosphatidylinositol 3-kinase (PI3K), NF-κB inhibitors, and IκB protease inhibitor. Stimulation of microglia with SDF-1α also increased Akt and ERK1/2 phosphorylation. In addition, SDF-1α treatment also increased IκB kinase α/β (IKK α/β) phosphorylation, IκBα phosphorylation, IκBα degradation, p65 phosphorylation at Ser 276, translocation of p65 and p50 from cytosol to nucleus and κB-luciferase activity. Moreover, SDF-1α-mediated increase of κB-luciferase activity was inhibited by pre-transfection of DN-p85, DN-Akt or DN-ERK2. Increase of IKK α/β phosphorylation and binding of p65 and p50 to the NF-κB element were both antagonized by PI3K and ERK inhibitors. Our results demonstrate a mechanism linking SDF-1α and IL-6, and provide additional support for the notion that SDF-1α plays a regulatory role in microglia activation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0014-2999eISSN: 1879-0712DOI: 10.1016/j.ejphar.2009.03.001Titel-ID: cdi_proquest_miscellaneous_67310993
- Format
- –
- Schlagworte
- Akt, Animals, Cell Line, Chemokine CXCL12 - metabolism, Chemokine CXCL12 - pharmacology, ERK, Extracellular Signal-Regulated MAP Kinases - metabolism, Humans, I-kappa B Kinase - metabolism, IL-6, Interleukin-6 - biosynthesis, Interleukin-6 - genetics, Intracellular Space - drug effects, Intracellular Space - metabolism, Mice, Microglia, Microglia - cytology, Microglia - drug effects, Microglia - metabolism, NF-kappa B - metabolism, NF-κB, Phosphatidylinositol 3-Kinases - metabolism, Phosphorylation, Proto-Oncogene Proteins c-akt - metabolism, Rats, Receptors, CXCR4 - metabolism, SDF-1α, Signal Transduction - drug effects, Up-Regulation - drug effects