| Role of Insulin in the Activation of NF-kappaB/IkappaB Pathway in Macrophage Cells. |
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Sang Min Lee, Yeon Sil Jang, Choon Taek Lee, Young Whan Kim, Sung Koo Han, Young Soo Shim, Chul Gyu Yoo |
1Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine, Seoul, Korea. cgyoo@snu.ac.kr
2Respiratory Center, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. |
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| Abstract |
BACKGROUND
Sepsis still has a high mortality rate despite adequate supportive care. Newer therapeutic modalities have been developed but they have generally ended in failure. Recently, insulin was reported to have an anti-inflammatory effect by inhibiting the IkappaB/NF-kappaB pathway, and may have therapeutic potential in sepsis. However, the precise mechanism of the anti-inflammatory effect of insulin is unclear. This study examined the role of insulin in activating IkappaB/NF-kappaB in macrophage. METHODS: Raw 264.7 cells, a murine macrophage cell line, were used in this experiment. Western blotting using IkappaB Ab and phosphor-specific IkappaB Ab was performed to evaluate the degradation and phosphorylation of IkappaB cells. For the IkappaB Kinase (IKK) activity, an immune complex kinase assay was performed. The level of interleukin-6 (IL-6) was measured by ELISA to determine the level of proinflammatory cytokine. RESULTS: IkappaBalpha degradation began 30 min after lipopolysaccharide (LPS) treatment. However, an insulin pretreatment suppressed the IkappaBalpha degradation caused by the LPS treatment. The phosphorylation of IkappaBalpha and IKK activity was also inhibited by the insulin pretreatment. Finally, the insulin pretreatment showed a tendency to suppress the induction of IL-6 by LPS. CONCLUSION: Insulin might have an anti-inflammatory effect though partial inhibition of the IkappaB/NFkappaB pathway in macrophage cell lines. |
| Key Words:
Insulin, Sepsis, Inflammation, NFkappaB |
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