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KMID : 0381120090310030251
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Genes and Genomics
2009 Volume.31 No. 3 p.251 ~ p.260
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The Glucosamine-Mediated Induction of CHOP Reduces the Expression of Inflammatory Cytokines by Modulating JNK and NF-κB in LPS-Stimulated RAW264.7 Cells
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Jeong Mini
Cho Jae-Wook
Cho Wang-Sik
Shin Gu-Choul
Lee Hyung-Hoan
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Abstract
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Macrophages secrete inflammatory cytokines and mono-nitrogen oxide (NO), and play crucial roles in inflammation in early-stage rheumatoid arthritis (RA). This study investigated whether glucosamine hydrochloride (GlcN), a nonsteroidal anti-inflammatory agent (NSAID) widely used to treat arthritis, affects the expression of inflammatory cytokines via the unfolded protein response (UPR) in lipopolysaccharide (LPS)-stimulated mouse macrophages (RAW264.7 cells). Pretreatment with GlcN reduced the expression of inflammatory cytokines and inhibited cell differentiation. Moreover, GlcN treatment increased the expression of CHOP and BiP/Grp78, the UPR target genes, in the presence or absence of LPS. Indeed, knockdown of CHOP using siRNAs prevented the GlcN-mediated reduction of inflammatory cytokines in LPS-stimulated RAW264.7 cells. Finally, we found that GlcN-mediated induction of CHOP reduced the phosphorylation of JNK and NF-κB in LPS-stimulated RAW264.7 cells. Combined, these results suggest that the GlcN-mediated induction of CHOP negatively regulates the inflammatory response by modulating JNK and NF-κB in LPS-stimulated RAW264.7 cells.
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KEYWORD
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inflammatory cytokines, ER stress, rheumatoid arthritis (RA), glucosamine, CHOP, JNK, RAW264.7 cells, unfolded protein response (UPR)
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