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Wilms, H; Schwark, T; Brandenburg, LO; Sievers, J; Dengler, R; Deuschl, G; Lucius, R.
Regulation of activin A synthesis in microglial cells: pathophysiological implications for bacterial meningitis.
J Neurosci Res. 2010; 88(1): 16-23.
Doi: 10.1002/jnr.22185
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
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Schwark Thorsten
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- Abstract:
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Previous studies have shown that activin A, a neuroprotective cytokine and dimeric polypeptide composed of two betaA subunits, is elevated in the cerebrospinal fluid of patients suffering from bacterial meningitis. In this study, to elucidate further the functional significance and pathophysiological implications of these findings, we demonstrated that microglial cells are not only the source but also the target cells of activin A in the central nervous system: immunohistochemistry and RT-PCR revealed expression of activin subunit betaA mRNA as well as activin receptor type I and type II mRNA in rat microglia in vitro. Further studies showed that activin enhances microglial proliferation and decreases the gamma-interferon-induced synthesis of nitric oxide, one of several microglial mediators involved in the inflammatory response in microglia activation. Furthermore, quantitative RT-PCR, Western blotting, and ELISA showed an inhibitory effect of activin on inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta gene and protein levels after lipopolysaccharide treatment. We suggest that the increased synthesis of activin A is directly involved, via influence on microglia cell functions, in the modulation of the inflammatory response in bacterial meningitis.
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Activin Receptors - genetics Activin Receptors - metabolism
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Activins - biosynthesis Activins - genetics
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Adolescent -
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Adult -
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Aged -
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Aged, 80 and over -
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Analysis of Variance -
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Animals -
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Blotting, Western -
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Cell Proliferation -
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Cells, Cultured -
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Cytokines - genetics Cytokines - metabolism
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Enzyme-Linked Immunosorbent Assay -
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Female -
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Humans -
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Immunohistochemistry -
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Interferon-gamma - pharmacology
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Lipopolysaccharides - pharmacology
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Male -
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Meningitis, Bacterial - genetics Meningitis, Bacterial - metabolism
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Meningitis, Viral - genetics Meningitis, Viral - metabolism
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Microglia - drug effects Microglia - metabolism
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Middle Aged -
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Nitric Oxide Synthase Type II - genetics Nitric Oxide Synthase Type II - metabolism
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RNA, Messenger - genetics RNA, Messenger - metabolism
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Rats -
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Rats, Wistar -
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Reverse Transcriptase Polymerase Chain Reaction -
- Find related publications in this database (Keywords)
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activin A
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cerebrospinal fluid
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ELISA
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meningitis
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microglia
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RT-PCR