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Release of activin A by microglial cells upon stimulation with bacterial TLR-agonists

Abstract number: o369

Ebert  S., Nau  R., Michel  U.

Objectives: 

Activin A, a member of the transforming growth factor-beta (TGF-beta) family of growth and differentiation factors, is a multifunctional cytokine, with one of its roles being in the immune system and inflammatory processes. Follistatin (FS) is a high affinity binding protein of activin and antagonises its actions. We previously demonstrated that concentrations of both activin and FS are elevated in the serum of patients with septicemia and in the cerebrospinal fluid (CSF) of patients with meningitis. The sources of the elevated concentrations of both proteins in CSF have not yet been discovered.

Methods: 

Primary mouse microglial cell cultures were exposed to the TLR agonists Pam3Cys (Tripalmitoyl-S-glyceryl-cysteine; TLR 2), endotoxin (LPS; TLR 4) and oligonucleotides containing unmethylated cytosin-guanosin motifs (CpG; TLR 9) for 24 hours in the presence of interferon-gamma (IFN-gamma; 100 U/ml). Concentrations of activin A and FS in the cell culture supernatants were measured by ELISA (R&D Systems GmbH). Mann-Whitney-U-test was performed to analyse differences in activin concentrations between groups (n = 10, respectively); p-values < 0.05 were considered statistically significant. Data are expressed as median (minimum/maximum).

Results: 

After treatment of microglial cultures with IFN-gamma alone (control group), activin A concentrations in the cell culture supernatant were below the detection limit of the ELISA. After combined treatment with IFN-gamma and one of the TLR-agonists, activin A concentrations in the cell culture supernatant were significantly elevated: 279 pg/ml (196/337) after treatment with 1 ug/ml LPS (p < 0.0001), 117 pg/ml (0/167) after treatment with 1 ug/ml Pam3Cys (p = 0.007), and 77 pg/ml (0/185) after treatment with 10 ug/ml CpG (p = 0.02). FS concentrations in all groups were below the detection limit of the ELISA.

Discussion: 

Our results show for the first time that microglial cells release activin A upon activation by bacterial TLR-agonists. This finding provides further evidence for a role of activin in the innate immune response and suggests that microglial cells are a source of elevated activin A concentrations observed in the CSF during bacterial meningitis.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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