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Abstracts (complete list) - Wissenschaft Online

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Thorsten Stroh, Arvind Batra, Rainer Glauben, Inka Fedke, Stephen Girardin, Martin<br />

Zeitz, Britta Siegmund<br />

Expression of NOD2 but not NOD1 is modulated by proinflammatory<br />

cytokines in murine preadipocytes<br />

Preadipocytes are linked to the innate immune system indicated by their expression of<br />

functional Toll-like receptors (TLR) and ability to phagocytosis. Recent studies of our<br />

group revealed the expression of members of the nucleotide-binding site and leucinerich<br />

repeat (NBS-LRR) proteins. These proteins belong to the family of intracellular<br />

pattern recognition receptors which act as sensors for motifs found in the<br />

peptidoglycans (PG) from bacteria. NOD1 binds to Lactyl-Tetra-DAP a peptidoglycan<br />

motif mainly found in PG from Gram-negative bacteria, NOD2 detects muramyl<br />

dipeptide (MDP) a motif contained in PG derived from Gram-positive bacteria.<br />

This study aimed to investigate the expression of NOD1 and NOD2 and their<br />

functionality in murine preadipocytes. Changes in expression were analysed after ligandspecific<br />

stimulation and stimulation with pro-inflammatory cytokines using quantitative<br />

real-time RT-PCR. Functionality of these receptors was tested by ligand-specific<br />

stimulation, and the subsequent response was evaluated by IL-6 production and<br />

activation of the NF-κB pathway. Specificity of stimulation was confirmed by RNA<br />

interference (RNAi) strategies. NOD1 mRNA was detectable in all samples. The<br />

expression was not altered after ligand–specific stimulation or stimulation with the<br />

proinflammatory cytokines IL-1β and TNFα. In contrast, NOD2 was slightly increased by<br />

NOD1-specific stimulation but could significantly be upregulated by stimulation with IL-<br />

1β. The strongest upregulation was observed after stimulation with LPS but different<br />

from stimulation with IL-1β or TNFα, LPS-induced upregulation was only present after<br />

4h of stimulation. Specific stimulation of NOD1 by LT-DAP resulted in a strong activation<br />

of the NF-κB pathway and a significant IL-6 production could be observed.<br />

Our data provide evidence that functional NBS-LRR proteins are expressed in<br />

preadipocytes and that expression of NOD2 can be modulated by pro-inflammatory<br />

cytokines. Thus underlining the position of preadipocytes in the innate immune system.

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