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It has been shown that glucosamine (GlcN) inhibits lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2) expression in macrophage. However, in this study, we demonstrated that GlcN enhanced the LPS-induced COX-2 expression in RAW 264.7 cells in low glucose cultured condition. It suggests that glucose concentration may be an important for LPS-induced COX-2 expression. We found that in low glucose condition, O-GlcNAc modification of Sp1 was increased by GlcN, although LPS did not further enhanced O-GlcNAc modification of Sp1. Further investigations regarding molecular mechanisms underlying the LPS-induced COX-2 expression and functional role of Sp1 transcription factor in the low glucose condition cultured RAW 264.7 cells.