Melatonin Suppresses LPS-Induced Oxidative Stress in Dendritic Cells for Inflammatory Regulation via the Nrf2/HO-1 Axis

Melatonin, an indoleamine synthesized in the pineal gland of mammals, is a natural bioactive compound with powerful antioxidant and anti-inflammatory properties. Here, we evaluated whether melatonin has the capacity to moderate the oxidative stress of dendritic cells (DCs) for inflammatory control in an acute lung injury (ALI) model. Our findings showed that melatonin remarkably inhibited total nitric oxide synthase (T-NOS) activity, nitric oxide (NO) production, intracellular reactive oxygen species (ROS) levels, and lipid peroxidation (MDA detection) levels in both an LPS-induced murine ALI model and LPS-induced DCs. Meanwhile, the reduced glutathione (GSH) level and the GSH/GSSG ratio were recovered. In addition, antioxidant enzymes, such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), were increased in these processes. Moreover, melatonin also inhibited the LPS-induced secretions of IL-1β, IL-6, and TGF-β in vivo and in vitro. Finally, we found that the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) axis was required in the inhibition of LPS-induced oxidative stress in DCs by melatonin. Altogether, these data indicate that melatonin strongly suppresses the LPS-induced oxidative stress in DCs, which is a promising DC-targeted strategy via inflammatory control for ALI treatment

<i>Holarrhena pubescens</i> Wall. ex G. Don Extracts Inhibit LPS-Irritated Oxidative Stress in Dendritic Cells

Holarrhena pubescens Wall. ex G. Don (H. pubescens), belonging to the Apocynaceae family, is distributed in deciduous forests of the tropical Himalayas. H. pubescens is an important traditional medicinal plant, especially its seeds and barks. Therefore, we assessed the antioxidant capacity of H. pubescens extracts in Lipopolysaccharide (LPS)-induced dendritic cells (DCs) for sepsis treatment. Our results indicated that H. pubescens extracts with different doses (25 μg/mL, 50 μg/mL, 100 μg/mL) reduced the reactive oxygen species (ROS) level, and weakened the nitric oxide synthases (NOS) activity and nitric oxide (NO) level in LPS (100 ng/mL)-irritated DCs. In addition, H. pubescens extracts decreased the oxidized glutathione (GSSG) production but increased the reduced glutathione (GSH) production, thereby preserving the cellular reductive status owing to the raised GSH/GSSG ratio. Furthermore, H. pubescens extracts strengthened the antioxidant enzymes activity in LPS-induced DCs, such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Finally, we found that H. pubescens extracts significantly improved the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the heme oxygenase 1 (HO–1) in LPS-irritated DCs. These results indicated that H. pubescens extracts suppressed the LPS-irritated oxidative stress in DCs via Nrf2/HO–1 signaling pathway, providing a potential strategy for sepsis therapy

Holarrhena pubescens Wall. ex G. Don Extracts Inhibit LPS-Irritated Oxidative Stress in Dendritic Cells

Holarrhena pubescens Wall. ex G. Don (H. pubescens), belonging to the Apocynaceae family, is distributed in deciduous forests of the tropical Himalayas. H. pubescens is an important traditional medicinal plant, especially its seeds and barks. Therefore, we assessed the antioxidant capacity of H. pubescens extracts in Lipopolysaccharide (LPS)-induced dendritic cells (DCs) for sepsis treatment. Our results indicated that H. pubescens extracts with different doses (25 &mu;g/mL, 50 &mu;g/mL, 100 &mu;g/mL) reduced the reactive oxygen species (ROS) level, and weakened the nitric oxide synthases (NOS) activity and nitric oxide (NO) level in LPS (100 ng/mL)-irritated DCs. In addition, H. pubescens extracts decreased the oxidized glutathione (GSSG) production but increased the reduced glutathione (GSH) production, thereby preserving the cellular reductive status owing to the raised GSH/GSSG ratio. Furthermore, H. pubescens extracts strengthened the antioxidant enzymes activity in LPS-induced DCs, such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Finally, we found that H. pubescens extracts significantly improved the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the heme oxygenase 1 (HO&ndash;1) in LPS-irritated DCs. These results indicated that H. pubescens extracts suppressed the LPS-irritated oxidative stress in DCs via Nrf2/HO&ndash;1 signaling pathway, providing a potential strategy for sepsis therapy

Riboflavin as a Mucosal Adjuvant for Nasal Influenza Vaccine

Intranasal immunization with whole inactivated virus (WIV) is an important strategy used for influenza prevention and control. However, a powerful mucosal adjuvant is required to improve nasal vaccine efficacy. Riboflavin, as a food additive with the advantages of being safe and low-cost, widely exists in living organisms. In this paper, the mucosal adjuvant function of riboflavin was studied. After intranasal immunization with H1N1 WIV plus riboflavin in mice, we found that the mucosal immunity based on the secretory IgA (sIgA) levels in the nasal cavity, trachea, and lung were strongly enhanced compared with H1N1 WIV alone. Meanwhile, the IgG, IgG1, and IgG2a levels in serum also showed a high upregulation and a decreased ratio of IgG1/IgG2a, which implied a bias in the cellular immune response. Moreover, riboflavin strongly improved the protection level of H1N1 inactivated vaccine from a lethal influenza challenge. Furthermore, riboflavin was found to possess the capacity to induce dendritic cell (DC) phenotypic (MHCII, CD40, CD80, and CD86) and functional maturation, including cytokine secretion (TNF-α, IL-1β, IL-12p70, and IL-10) and the proliferation of allogeneic T cells. Lastly, we found that the DC maturation induced by riboflavin was dependent on the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which plays an important role in immune regulation. Therefore, riboflavin is expected to be developed as an alternative mucosal adjuvant for influenza nasal vaccine application

Astaxanthin Protects Dendritic Cells from Lipopolysaccharide-Induced Immune Dysfunction

Astaxanthin, originating from seafood, is a naturally occurring red carotenoid pigment. Previous studies have focused on its antioxidant properties; however, whether astaxanthin possesses a desired anti-inflammatory characteristic to regulate the dendritic cells (DCs) for sepsis therapy remains unknown. Here, we explored the effects of astaxanthin on the immune functions of murine DCs. Our results showed that astaxanthin reduced the expressions of LPS-induced inflammatory cytokines (TNF-α, IL-6, and IL-10) and phenotypic markers (MHCII, CD40, CD80, and CD86) by DCs. Moreover, astaxanthin promoted the endocytosis levels in LPS-treated DCs, and hindered the LPS-induced migration of DCs via downregulating CCR7 expression, and then abrogated allogeneic T cell proliferation. Furthermore, we found that astaxanthin inhibited the immune dysfunction of DCs induced by LPS via the activation of the HO-1/Nrf2 axis. Finally, astaxanthin with oral administration remarkably enhanced the survival rate of LPS-challenged mice. These data showed a new approach of astaxanthin for potential sepsis treatment through avoiding the immune dysfunction of DCs

Astaxanthin Provides Antioxidant Protection in LPS-Induced Dendritic Cells for Inflammatory Control

Astaxanthin, originating from marine organisms, is a natural bioactive compound with powerful antioxidant activity. Here, we evaluated the antioxidant ability of astaxanthin on dendritic cells (DCs), a key target of immune regulation, for inflammatory control in a sepsis model. Our results showed that astaxanthin suppressed nitric oxide (NO) production, reactive oxygen species (ROS) production, and lipid peroxidation activities in LPS-induced DCs and LPS-challenged mice. Moreover, the reduced glutathione (GSH) levels and the GSH/GSSG ratio were increased, suggesting that astaxanthin elevated the level of cellular reductive status. Meanwhile, the activities of antioxidant enzymes, including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), were significantly upregulated. Astaxanthin also inhibited the LPS-induced secretions of IL-1β, IL-17, and TGF-β cytokines. Finally, we found that the expressions of heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly upregulated by astaxanthin in LPS-induced DCs, suggesting that the HO-1/Nrf2 pathway plays a significant role in the suppression of oxidative stress. These results suggested that astaxanthin possesses strong antioxidant characteristics in DC-related inflammatory responses, which is expected to have potential as a method of sepsis treatment