Effects of alpha-mangostin on the expression of anti-inflammatory genes in U937 cells

• Main Authors: Liu Szu-Hsiu, Lee Lain-Tze, Hu Nai-Yun, Huange Kuo-Kuei, Shih Ying-Chu, Munekazu Iinuma, Li Jen-Ming, Chou Ting-Yu, Wang Wei-Hsin, Chen Ting-Shou
• Format: Article
• Language: English
• Published: BMC 2012-08-01
• Series: Chinese Medicine
• Online Access: http://www.cmjournal.org/content/7/1/19

<p>Abstract</p> <p>Background</p> <p>α-Mangostin (α-MG) is a main constituent of the fruit hull of the mangosteen. Previous studies have shown that α-MG has pharmacological activities such as antioxidant, antitumor, anti-inflammatory, antiallergic, antibacterial, antifungal and antiviral effects. This study aims to investigate the anti-inflammatory molecular action of α-MG on gene expression profiles.</p> <p>Methods</p> <p>U937 and EL4 cells were treated with different concentrations of α-MG in the presence of 0.1 ng/mL lipopolysaccharide (LPS) for 4 h. The anti-inflammatory effects of α-MG were measured by the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-4 in cell culture media, which were determined with enzyme-linked immunosorbent assay kits. The gene expression profiles of all samples were analyzed with a whole human genome microarray, Illumina BeadChip WG-6 version 3, containing 48804 probes. The protein levels were determined by Western blotting analyses.</p> <p>Results</p> <p>α-MG decreased the LPS induction of the inflammatory cytokines TNF-α (<it>P</it> = 0.038) and IL-4 (<it>P</it> = 0.04). α-MG decreased the gene expressions in oncostatin M signaling <it>via</it> mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinases (<it>P</it> = 0.016), c-Jun N-terminal kinase (<it>P</it> = 0.01) , and p38 (<it>P</it> = 0.008). α-MG treatment of U937 cells reduced the phosphorylation of MAPK kinase 3 / MAPK kinase 6 (<it>P</it> = 0.0441), MAPK-activated protein kinase-2 (<it>P</it> = 0.0453), signal transducers and activators of transcription-1 (STAT1) (<it>P</it> = 0.0012), c-Fos (<it>P</it> = 0.04), c-Jun (<it>P</it> = 0.019) and Ets-like molecule 1 (Elk-1) (<it>P</it> = 0.038).</p> <p>Conclusion</p> <p>This study demonstrates that α-MG attenuates LPS-mediated activation of MAPK, STAT1, c-Fos, c-Jun and EIK-1, inhibiting TNF-α and IL-4 production in U937 cells.</p>