High Glucose Stimulates TNFα and MCP-1 Expression in Rat Microglia Via ROS and NF-κB Pathways

Overview

Journal Acta Pharmacol Sin

Specialty Pharmacology

Date 2011 Feb 5

PMID 21293471

Citations 55

Authors

Yi Quan

Chang-Tao Jiang

Bing Xue

Shi-Gong Zhu

Xian Wang

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate whether high glucose stimulates the expression of inflammatory cytokines and the possible mechanisms involved.

Methods: ELISA and real-time PCR were used to determine the expression of the inflammatory factors, and a chemiluminescence assay was used to measure the production of reactive oxygen species (ROS).

Results: Compared to low glucose (10 mmol/L), treatment with high glucose (35 mmol/L) increased the secretion of tumor necrosis factor (TNF)α and monocyte chemotactic protein-1 (MCP-1), but not interleukin (IL)-1β and IL-6, in a time-dependent manner in primary cultured rat microglia. The mRNA expression of TNFα and MCP-1 also increased in response to high glucose. This upregulation was specific to high glucose because it was not observed in the osmotic control. High-glucose treatment stimulated the formation of ROS. Furthermore, treatment with the ROS scavenger NAC significantly reduced the high glucose-induced TNFα and MCP-1 secretion. In addition, the nuclear factor kappa B (NF-κB) inhibitors MG132 and PDTC completely blocked the high glucose-induced TNFα and MCP-1 secretion.

Conclusion: We found that high glucose induces TNFα and MCP-1 secretion as well as mRNA expression in rat microglia in vitro, and this effect is mediated by the ROS and NF-κB pathways.

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