Ghodratollah Panahi1, Parvin Pasalar1, Mina Zare2, Rosario Rizzuto3, Reza Meshkani1. 1. a Department of Biochemistry, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran. 2. b Recombinant Protein Laboratory, Department of Biochemistry , Shiraz University of Medical Sciences , Shiraz , Iran. 3. c Department of Biomedical Sciences , University of Padova , Padua , Italy.
Abstract
OBJECTIVE: The aim of this study was to investigate the effects of high glucose (HG) on inflammation in HepG2 cells. METHODS: The molecular mechanisms linking HG to inflammation was assessed in HepG2 cells exposed to HG (33 mM). RESULTS: The results showed that HG significantly enhanced TNF-α, IL-6 and PAI-1 expression in HepG2 cells. Increased expression of cytokines was accompanied by enhanced phosphorylation of JNK, P38, ERK and IKKα/IKKβ. In addition, JNK, ERK, P38 and NF-kB inhibitors could significantly attenuate HG-induced expression of TNF-α, IL-6 and PAI-1. Furthermore, HG could promote the generation of reactive oxygen species (ROS), while N-acetyl cysteine, a ROS scavenger, had an inhibitory effect on the expression of TNF-α, IL-6 and PAI-1 in HG-treated cells. CONCLUSIONS: Our results indicated that HG-induced inflammation is mediated through the generation of ROS and activation of the MAPKs and NF-kB signalling pathways in HepG2 cells.
OBJECTIVE: The aim of this study was to investigate the effects of high glucose (HG) on inflammation in HepG2 cells. METHODS: The molecular mechanisms linking HG to inflammation was assessed in HepG2 cells exposed to HG (33 mM). RESULTS: The results showed that HG significantly enhanced TNF-α, IL-6 and PAI-1 expression in HepG2 cells. Increased expression of cytokines was accompanied by enhanced phosphorylation of JNK, P38, ERK and IKKα/IKKβ. In addition, JNK, ERK, P38 and NF-kB inhibitors could significantly attenuate HG-induced expression of TNF-α, IL-6 and PAI-1. Furthermore, HG could promote the generation of reactive oxygen species (ROS), while N-acetyl cysteine, a ROS scavenger, had an inhibitory effect on the expression of TNF-α, IL-6 and PAI-1 in HG-treated cells. CONCLUSIONS: Our results indicated that HG-induced inflammation is mediated through the generation of ROS and activation of the MAPKs and NF-kB signalling pathways in HepG2 cells.