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KMID : 0928520100200020234
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Korean Journal of Lipidology
2010 Volume.20 No. 2 p.234 ~ p.244
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Stimulation of GITR Induces the Expression of TGF-β-inducible Gene h3 (βig-h3) through ERK and PI3K in THP-1 Cells
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Lee Seung-hee
Lee Min-Young
Suk Kyoung-Ho
Kim In-San
Lee Won-Ha
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Abstract
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Background: Glucocorticoid-induced TNF receptor-related protein (GITR), also known as AITR or TNFRSF18, is involved in pathogenesis of inflammatory diseases such as atherosclerosis and rheumatoid arthritis. TGF-β -inducible gene h3 (βig-h3), an extracellular matrix protein whose expression is regulated by TGF-β, is involved in cellular growth, differentiation, adhesion, migration, and angiogenesis. Although various stimuli have been shown to induce the expression of βig-h3, the regulation of its expression by GITR has not been defined. In order to investigate the expression pattern of βig-h3 and the associated signaling pathways, the human macrophage-like cell line THP-1 was analyzed after stimulation of GITR.
Methods: THP-1 cells were stimulated with monoclonal antibody (mAb) against GITR, along with other stimuli such as lipopolysaccharide and mAbs against other members of TNF superfamily. The expression patterns of βig-h3 and associated signaling pathways were analyzed using Western blot and RT-PCR analysis.
Results: Stimulation of THP-1 cells with mAb against GITR, along with other stimuli, induced the expression and secretion of βig-h3. Utilization of various inhibitors and Western blot analysis revealed that PKC, ERK and PI3K mediated the GITR-mediated signaling pathway and that NF-κB was responsible for the expression of βig-h3.
Conclusion: GITR-mediated inflammatory changes in THP-1 cells can induce the expression of βig-h3 via transcriptional activation of its gene. GITR may contribute to the pathogenesis of chronic inflammatory diseases through modulation of the expression of βig-h3 and consequently its function.
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KEYWORD
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GITR, βig-H3, Macrophage, Inflammation, Signaling
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