interleukin-8 and astaxanthine

Although extracellular carbonylated proteins (CPs) are found at higher levels in sun-exposed skin, their impact on the cellular functions of fibroblasts and their involvement in the progression of photoaging skin are not fully clarified. In our previous study, we reported that extracellular CPs increase levels of intracellular oxidative stress and result in the accumulation of newly synthesized CPs in normal human dermal fibroblasts (NHDF). Furthermore, fibroblasts exposed to CP-BSA, which is a model of extracellular CPs, had upregulated expression levels of mRNAs encoding matrix metalloproteinase-1 (MMP-1) and interleukin-8/CXCL8 (IL-8/CXCL8). These facts suggested the possibility that extracellular CPs induce a fragile structure in the dermis through the degradation of collagen and elastin. The purpose of this study was to characterize the efficacy of natural carotenoids, such as astaxanthin analogs, produced by Hematococus pluvialis (CHPs) to improve the impaired functions of fibroblasts exposed to CPs. CHPs suppressed the intracellular CP levels elevated by CP-BSA, restored mRNA expression levels of factors involved in the formation and assembly of collagen and elastin fibers and improved the formation of those fibers impaired by CP-BSA. We conclude that CHPs function as antiaging substances due to their restoration of the impaired formation of collagen and elastin fibers caused by extracellular soluble CPs.

Topics: Cells, Cultured; Collagen; Dermis; Elastin; Fibroblasts; Gene Expression; Humans; Interleukin-8; Matrix Metalloproteinase 1; Oxidative Stress; Protein Carbonylation; RNA, Messenger; Skin Aging; Xanthophylls

The anti-inflammatory effects and cellular transport mechanisms of all- E-astaxanthin and its 9Z- and 13Z-isomers were investigated in a Caco-2 cell monolayer model. All three astaxanthin isomers at 1.2 μM significantly reduced the TNF-α-induced secretion of IL-8 by 22-27%. Z-Astaxanthins, especially 9 Z-astaxanthin exhibited greater anti-inflammatory effect than all- E-astaxanthin by down-regulating pro-inflammatory cytokines COX-2 and TNF-α gene expression to 0.88 ± 0.01-fold and 0.83 ± 0.17-fold that of the negative control (NC), respectively. The anti-inflammatory effects of astaxanthin isomers were achieved via modulating the NF-κB signaling pathway as they down-regulated TNF-α-induced phosphorylation of IκBα from 5.3 ± 0.19-fold to 3.8 ± 0.33-4.5 ± 0.27-fold of NC. The scavenger receptor class B type I protein (SR-BI) was found to facilitate the cellular uptake of astaxanthin isomers. Its inhibitor (BLT-1) and antibody (Anti-SRBI) significantly reduced cellular uptake efficiency of all- E-astaxanthin (18.9% and 16.7%, respectively) and 13Z-astaxanthin (28.8% and 30.2%, respectively), but not of 9Z-astaxanthin. The molecular docking experiment showed that 13 Z-astaxanthin had significantly higher affinity with SR-BI (atomic contact energy: -420.31) than all- E-astaxanthin and 9 Z-astaxanthin, which at least partially supports the higher bioavailability of 13 Z-astaxanthin observed in vivo by others.

Topics: Anti-Inflammatory Agents; Biological Transport; Caco-2 Cells; Cell Membrane; Humans; Interleukin-8; Intestinal Mucosa; Isomerism; Molecular Docking Simulation; NF-kappa B; Scavenger Receptors, Class B; Signal Transduction; Tumor Necrosis Factor-alpha; Xanthophylls

Topics: Adenosine Triphosphate; Antioxidants; Cell Line, Tumor; Epithelial Cells; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Host-Pathogen Interactions; Humans; Interleukin-8; Membrane Potential, Mitochondrial; Mitochondria; NF-kappa B; Oxidative Stress; PPAR gamma; Reactive Oxygen Species; Signal Transduction; Xanthophylls

To elucidate the effects of redox balance regulation on cutaneous inflammation, we used the potent antioxidant astaxanthin (AX) to assess its effect on the UVB-induced secretion of PGE(2) and IL-8 in human keratinocytes and analysed its biological mechanism of action. The addition of AX (at 8 μm) to human keratinocytes even after UVB irradiation significantly down-regulated the increased secretion of PGE(2) or IL-8. Those suppressive effects were accompanied by significantly decreased expression of genes encoding COX-2 or IL-8 as well as COX-2 protein. Analysis using a specific NF-κB tanslocation inhibitor demonstrated that the UVB-stimulated secretion of PGE(2) and IL-8 was significantly abolished by its treatment prior to UVB irradiation. Western blotting of phosphorylated signalling molecules revealed that UVB irradiation (80 mJ/cm(2) ) significantly stimulated the phosphorylation of p38, ERK and JNK, which was not suppressed by treatment with AX after irradiation. In contrast, AX significantly inhibited the UVB-increased phosphorylation of mitogen- and stress-activated protein kinase (MSK)-1, NF-kBp65 or CREB even when treated postirradiation. Further, the MSK1 inhibitor H89 significantly down-regulated the increased secretion of PGE(2) and IL-8 in UVB-exposed human keratinocytes, following post-irradiation treatment. These findings suggests that AX attenuates the auto-phosphorylation of MSK1 required for its activation, which results in the decreased phosphorylation of NF-kBp65, which in turn probably leads to a deficiency of NF-kB DNA binding activity. This may be associated with the significant suppression of PGE(2) /IL-8 secretion via the down-regulated expression of COX-2 and IL-8 at the gene and/or protein levels.

Topics: Cyclooxygenase 2; Dinoprostone; Down-Regulation; Enzyme Inhibitors; Humans; Interleukin-8; Isoquinolines; Keratinocytes; Microscopy, Confocal; Models, Biological; Phosphorylation; Reactive Oxygen Species; Ribosomal Protein S6 Kinases, 90-kDa; Signal Transduction; Sulfonamides; Ultraviolet Rays; Xanthophylls