Poster presentation, P125

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Inhibition of eotaxin-1/CCL11 expression by novel compound in mouse embryonic fibroblast

BACKGROUND AND OBJECTIVES: The chemokines are a large family of small proteins involved in the activation and recruitment of specific cell populations during the course of disease. CCL11, a CC chemokine, is a potent chemoattractant and an activator of eosinophils, basophils, and Th2 lymphocytes. CCL11 expression was found to be restricted to a few cell types, including eosinophils, bronchial epithelial cells, and dermal fibroblast cells. In asthmatics, the expression of CCL11 has been found to be enhanced in these types of cells, and increased expression is associated with disease severity. Additionally, CCL11 expression in epithelial cells was found to be increased in atopic dermatitis, as well as in other inflammatory conditions. This study was aimed to investigate effects of BSP-3 on expression of CCL11 induced by TNF-a and its action mechanisms in fibroblasts. METHODS: In order to determine the effects of BSP-3 on TNF-a-induced expression of CCL11, we performed enzyme-linked immunosorbent assay and quantitative RT-PCR for CCL11 and a western blot assay for activation of MAPKs. The transient luciferase reporter was used to examine activation of transcription factors. RESULTS: In our NF-kB luciferase reporter system, TNF-alpha-induced NF-kB activation was observed to be reduced by BSP-3 (a dicarboxylic acid). In accordance with this result, BSP-3 also inhibited TNF-alpha-induced phosphorylation and degradation of IkB-a. as well as nuclear translocation of NF-kB heterodimer induced by TNF-alpha. This suggests that BSP-3 downregulates the expression of CCL11 via the inhibition of NF-kB activation signaling. Using the NF-kB luciferase reporter system, Western blot analysis, and IKK-beta activity assay, we determined that BSP-3 inhibits IKK-beta activity in NF-kB signaling, which upregulates the expression of CCL11. CONCLUSION: Our results show that BSP-3 inhibits the expression of CCL11 by suppressing the IKK-beta activity in NF-kB activation signaling.

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