Essential role of Toll-like receptor 2 in macrophage activation by glycogen
| Autor: | Naohito Ohno, Yoshiyuki Adachi, Takashi Kuriki, Ryo Kakutani, Hiroki Takata |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Lipopolysaccharides
MAP Kinase Signaling System Biology Nitric Oxide Biochemistry Proinflammatory cytokine Gene Knockout Techniques Mice chemistry.chemical_compound Genes Reporter Animals Humans Phosphorylation Receptor Luciferases Renilla Mice Inbred BALB C Toll-like receptor Innate immune system Glycogen Macrophages NF-kappa B Macrophage Activation Immunity Innate Toll-Like Receptor 2 Cell biology Mice Inbred C57BL Toll-Like Receptor 4 TLR2 HEK293 Cells chemistry TLR3 TLR4 Cytokines Protein Binding |
| Zdroj: | Glycobiology. 22:146-159 |
| ISSN: | 1460-2423 0959-6658 |
| DOI: | 10.1093/glycob/cwr122 |
| Popis: | We prepared enzymatically synthesized glycogen (ESG) with the same characteristics as natural glycogen and investigated whether the macrophage-stimulating activity of glycogen was related to Toll-like receptors (TLRs), which are important receptors for innate immunity. ESG induced no nuclear factor-kappa B (NF-κB) activity in TLR4/MD-2/CD14-expressed human embryonic kidney 293 (HEK293) reporter cells, whereas this polysaccharide did activate peritoneal exude cells (PECs) derived from TLR4-deficient mice at the same level as those from wild-type (WT) mice. Similarly, ESG did not activate HEK293 cells expressing TLR3, 5, 7, 8 or 9, suggesting that these TLRs were irrelevant to the activity of ESG. In contrast, ESG enhanced the NF-κB activity of TLR2-expressed HEK293 reporter cells in a concentration-dependent manner. Furthermore, the cell-stimulating activity of ESG was remarkably lower for PECs from TLR2-deficient mice compared with those from WT mice. The activity of ESG completely disappeared after treatment with a glycogen-degrading enzyme, indicating that the activity derived from ESG itself and not from contamination with canonical TLR2 ligands such as bacterial lipopeptides. Moreover, it was clarified by ELISA that ESG was directly bound to TLR2. Taken together, these results demonstrated that TLR2 directly recognizes glycogen and that the recognition activates immunocytes such as macrophages to enhance the production of nitric oxide and inflammatory cytokines. In addition, it was suggested that TLR2 could be involved in the glycogen activity in vivo. We propose that glycogen act as an activator to potentiate the host defense through TLR2 on the macrophage. |
| Databáze: | OpenAIRE |
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