Inhibition of Cytokine Release by Mycobacterium tuberculosis Phenolic Glycolipid Analogues |
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Authors: | Dr. Hassan R. H. Elsaidi Dr. Todd L. Lowary |
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Affiliation: | Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Gunning‐Lemieux Chemistry Centre, 11225 Saskatchewan Drive, Edmonton, AB T6G 2G2 (Canada) |
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Abstract: | Infection by Mycobacterium tuberculosis causes tuberculosis, a disease characterized by alteration of host innate and adaptive immunity. These processes are mediated by a series of bacterial biomolecules, among which phenolic glycolipids (PGLs) and the related p‐hydroxybenzoic acid derivatives have been suggested to play important roles. To probe the importance of structural features of these glycans on cytokine modulation, we synthesized three M. tuberculosis PGL analogues ( 1 – 3 ), which differ from the native glycoconjugates by possessing a simplified lipid algycone. The ability of 1 – 3 to modulate the release of proinflammatory cytokines (TNF‐α, IL‐1β, IL‐6, MCP‐1) and nitric oxide (NO) was evaluated. None of the compounds stimulated the secretion of these signalling molecules. However, all showed a Toll‐like Receptor 2‐mediated, concentration‐dependent inhibition profile that was related to the methylation pattern on the glycan. |
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Keywords: | cytokines glycolipids immunomodulators mycobacteria Toll‐like receptors tuberculosis |
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