Skip to main content

Advertisement

The Damage Associated Molecular Pattern (DAMP) molecule S100A12 induces pro-inflammatory responses in monocytes via innate immunity signalling pathways

Article metrics

  • 1864 Accesses

  • 1 Citations

Background

In a previous study, we demonstrated excessive activation of neutrophils leading to high concentrations of S100A12, a member of the damage-associated molecular pattern molecules (DAMP), in systemic-onset juvenile idiopathic arthritis (SOJIA) which is not found in other inflammatory diseases. Binding to the Receptor for Advanced Glycation Endproducts (RAGE) has been shown but exact molecular mechanisms of S100A12 leading to pro-inflammatory responses in immune cells are still lacking.

Methods

We analyzed the S100A12-induced expression pattern in human monocytes by microarray technology. Results were independently confirmed by real-time polymerase chain reaction (PCR) and flow cytometry. Additionally we used different knock down approaches of signalling pathways to identify common inflammatory and ligand-specific effects on gene expression changes.

Results

Functional clustering indicated induction of monocytic properties such as pro-inflammatory activation, chemotaxis, and repression of apoptosis. 43% of 745 S100A12-induced genes are also up-regulated by LPS already indicating a strong overlap. Inhibition revealed TLR-4 and NFκB as key signalling pathways.

Conclusion

In terms of gene expression changes S100A12 shows strong overlaps with LPS. Similar to LPS a significant portion of gene expression changes induced by S100A12 are dependent on TLR4 and NF-kB. Additionally, S100A12 activates an at least second strong signalling pathway which might be a RAGE-dependent cascade.

Author information

Correspondence to H Wittkowski.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Wittkowski, H., Viemann, D., Lueken, A. et al. The Damage Associated Molecular Pattern (DAMP) molecule S100A12 induces pro-inflammatory responses in monocytes via innate immunity signalling pathways. Pediatr Rheumatol 6, P2 (2008) doi:10.1186/1546-0096-6-S1-P2

Download citation

Keywords

  • Juvenile Idiopathic Arthritis
  • Gene Expression Change
  • Human Monocyte
  • Excessive Activation
  • Immunity Signalling