Down-regulation of IL-6 production by astaxanthin via ERK-, MSK-, and NF-kappa B-mediated signals in activated microglia

作者：Kim Yeon Hyang^*; Koh Hyung Kon; Kim Doo Sik

来源：International Immunopharmacology, 2010, 10(12): 1560-1572.

DOI：10.1016/j.intimp.2010.09.007

• Astaxanthin
• IL-6
• ERK1/2
• MSK
• NF-kappa B
• Microglia

In this study, we investigated the effect of astaxanthin on IL-6 in activated microglial cells because excessive interleukin-6 (IL-6) production by activated brain microglia has been linked to many neurological disorders and proper regulation of IL-6 is critical for maintaining brain homeostasis. Astaxanthin inhibited lipopolysaccharide (LPS)-stimulated IL-6 mRNA and protein in BV-2 microglial cells. Moreover, LPS-induced p-IKK alpha, p-I kappa B alpha, and p-NF-kappa B p65 levels were all suppressed by astaxanthin. The translocation of p-NF-kappa B p65 from the cytosol into the nucleus and transcriptional activity were inhibited by astaxanthin. IL-6 expression and NF-kappa B transcriptional activation were inhibited by astaxanthin, as well as inhibitors of NF-kappa B and MAPK in LPS-stimulated BV-2 microglial cells. Consistent with these findings, astaxanthin down-regulated the activation of p-extracellular signal-regulated kinase 1/2 (p-ERK1/2) and p-mitogen- and stress-activated protein kinase 1 (p-MSK1), but not of p-c-jun N-terminal kinase (p-JNK). Astaxathin also decreased IL-6 mRNA and protein levels in LPS-stimulated primary microglial cells, RAW264.7 macrophages, and peritoneal macrophages. In addition, IL-6 suppression through astaxanthin-induced down-regulation of p-ERK1/2, p-MSK1, and p-NF-kappa B p65 occurred in microglial cells stimulated with LPS or stromal derived factor (SDF)-1 alpha. Astaxathin also inhibited the secretion and mRNA expression of IL-6 in SDF-1 alpha-stimulated microglial cells. SDF-1 alpha-stimulated ERK1/2, MSK1, and NF-kappa B p65 phosphorylation were reduced by astaxanthin. Therefore, our results suggest that astaxanthin regulates IL-6 production through a p-ERK1/2-MSK-1- and p-NF-kappa B p65-dependent pathway in activated microglial cells.

• 出版日期2010-12