Mesangial cells of lupus-prone mice are sensitive to chemokine production

Infectious antigens may be triggers for the exacerbation of systemic lupus erythematosus. The underlying mechanism causing acceleration and exacerbation of lupus nephritis (LN) is largely unknown. Bacterial lipopolysaccharide (LPS) is capable of inducing an accelerated model of LN in NZB/W mice, featuring diffuse proliferation of glomerular resident cells. We hypothesized that mesangial cells (MCs) from LN subjects are more responsive to LPS than normal subjects. Cultured primary NZB/W and DBA/W (nonautoimmune disease-prone strain with MHC class II molecules identical to those of NZB/W) MCs were used. Monocyte chemoattractant protein-1 (MCP-1) and osteopontin (OPN) expressions either in the baseline (normal culture) condition or in the presence of LPS were evaluated by real-time PCR, ELISA, or western blot analysis. NF-κB was detected by ELISA, electrophoresis mobility-shift assay, and immunofluorescence. First, either in the baseline condition or in the presence of LPS, NZB/W MCs produced significantly higher levels of MCP-1 and OPN than the DBA/W MC controls. Second, NZB/W MCs expressed significantly higher levels of Toll-like receptor 4, myeloid differentiation factor 88, and NF-κB than the DBA/W MC controls, both receiving exactly the same LPS treatment. In conclusion, NZB/W MCs are significantly more sensitive than their normal control DBA/W MCs in producing both MCP-1 and OPN. With LPS treatment, the significantly elevated levels of both chemokines produced by NZB/W MCs are more likely due to a significantly greater activation of the Toll-like receptor 4-myeloid differentiation factor 88-associated NF-κB pathway. The observed abnormal molecular events provide an intrarenal pathogenic pathway involved in an accelerated type of LN, which is potentially infection triggered

The effect of caffeic acid phenethyl ester on the functions of human monocyte-derived dendritic cells

<p>Abstract</p> <p>Background</p> <p>Propolis, an ancient herbal medicine, has been reported the beneficial effect both in asthma patients and murine model of asthma, but the mechanism was not clearly understood. In this study, the effect of caffeic acid phenethyl ester (CAPE), the most extensively studied components in propolis, on the functions of human monocyte-derived dendritic cells (MoDCs) was investigated.</p> <p>Results</p> <p>CAPE significantly inhibited IL-12 p40, IL-12 p70, IL-10 protein expression in mature healthy human MoDCs stimulated by lipopolysaccharides (LPS) and IL-12 p40, IL-10, IP-10 stimulated by crude mite extract. CAPE significantly inhibited IL-10 and IP-10 but not IL-12 expression in allergic patients' MoDCs stimulated by crude mite extract. In contrast, the upregulation of costimulatory molecules in mature MoDCs was not suppressed by CAPE. Further, the antigen presenting ability of DCs was not inhibited by CAPE. CAPE inhibited IκBα phosphorylation and NF-κB activation but not mitogen-activated protein kinase (MAPK) family phosphorylation in human MoDCs.</p> <p>Conclusion</p> <p>These results indicated that CAPE inhibited cytokine and chemokine production by MoDCs which might be related to the NF-κB signaling pathway. This study provided a new insight into the mechanism of CAPE in immune response and the rationale for propolis in the treatment of asthma and other allergic disorders.</p

The Lanostane Triterpenoids in Poria cocos Play Beneficial Roles in Immunoregulatory Activity

Poria cocos (Schwein) F.A. Wolf (syn. Wolfiporia cocos) dried sclerotium, called fuling, is an edible, saprophytic fungus commonly used as a tonic and anti-aging traditional Chinese medicine. It is traditionally used in combination with other traditional Chinese medicines to enhance immunity. This study showed that P. cocos extract (Lipucan®) containing lanostane triterpenoids has no immunotoxicity and enhances non-specific (innate) immunity though activating natural killer cells and promotes interferon γ (IFN-γ) secretion by Type 1 T-helper (Th1) cells immune response. In addition, P. cocos extract significantly decreased interleukin (IL-4 and IL-5) secretion by Type 2 T-helper (Th2) cells immune response, which are related to the allergy response. The purified lanostane triterpenoids were first identified as active ingredients of P. cocos with enhanced non-specific immunity by promoting interferon γ (IFN-γ) secretion in a preliminary study. Our findings support that the P. cocos extract plays beneficial roles in immunoregulatory activity

The Lanostane Triterpenoids in <i>Poria cocos</i> Play Beneficial Roles in Immunoregulatory Activity

Poria cocos (Schwein) F.A. Wolf (syn. Wolfiporia cocos) dried sclerotium, called fuling, is an edible, saprophytic fungus commonly used as a tonic and anti-aging traditional Chinese medicine. It is traditionally used in combination with other traditional Chinese medicines to enhance immunity. This study showed that P. cocos extract (Lipucan®) containing lanostane triterpenoids has no immunotoxicity and enhances non-specific (innate) immunity though activating natural killer cells and promotes interferon γ (IFN-γ) secretion by Type 1 T-helper (Th1) cells immune response. In addition, P. cocos extract significantly decreased interleukin (IL-4 and IL-5) secretion by Type 2 T-helper (Th2) cells immune response, which are related to the allergy response. The purified lanostane triterpenoids were first identified as active ingredients of P. cocos with enhanced non-specific immunity by promoting interferon γ (IFN-γ) secretion in a preliminary study. Our findings support that the P. cocos extract plays beneficial roles in immunoregulatory activity

The Immunoregulatory Effects of Caffeic Acid Phenethyl Ester on the Cytokine Secretion of Peripheral Blood Mononuclear Cells From Asthmatic Children

Asthma is a chronic inflammatory disease of the airways for which current treatments are mainly based on pharmacological interventions, such as glucocorticoid therapy. Our objective was to study the immunoregulatory effects of caffeic acid phenethyl ester (CAPE, a phytochemical synthesized from propolis) on cytokine secretion of peripheral blood mononuclear cells (PBMCs) from asthmatic children. Methods: PBMCs from asthmatic children (5.5±3.3 years old, n=28) and healthy children (5.6±2.8 years old, n=23) were co-cultured with CAPE in vitro with and without phorbol-12-myristate-13-acetate-ionomycin. Results: Our results show that predominant interleukin 4 (IL-4) and interferon-gamma secretion of cultured supernatant were detected in healthy donors compared with asthmatics. In the presence of phorbol-12-myristate-13-acetate-ionomycin, with or without CAPE treatment, the asthmatic children showed significantly decreased levels of IL-10 secretion compared with the healthy controls. However, CAPE significantly decreased IL-10 and interferon-gamma in healthy donors. There was a slight but not statistically significant reduction of IL-4 secretion in CAPE-treated PBMCs compared with untreated control PBMCs from the healthy children. Our data also shows that CAPE significantly enhanced transforming growth factor-beta 1 production from PBMCs from asthmatic children. Conclusion: The immunoregulatory effects of CAPE on human PBMCs may be through the induction of regulatory T cells, as evidenced by the enhanced transforming growth factor-beta 1 production from PBMCs from asthmatic children in our study

Plant-Based, Antioxidant-Rich Snacks Elevate Plasma Antioxidant Ability and Alter Gut Bacterial Composition in Older Adults

Plant-rich diets alleviate oxidative stress and gut dysbiosis and are negatively linked to age-associated chronic disorders. This study examined the effects of consuming plant-based, antioxidant-rich smoothies and sesame seed snacks (PBASS) on antioxidant ability and gut microbial composition in older adults. Healthy and sub-healthy older adults (n = 42, 79.7 ± 8.6 years old) in two senior living facilities were given PBASS for 4 months. Blood and fecal samples were collected from these individuals at the baseline and after 2 and 4 months of PBASS consumption. After 2 months, serum levels of albumin and high-density lipoprotein-cholesterol and the ratio of reduced to oxidized glutathione (GSH/GSSG) had increased significantly and erythrocytic glutathione, GSH/GSSG and superoxide dismutase activity had decreased significantly compared with baseline levels (p &lt; 0.05). After 4 months, red blood cells, hematocrit, serum blood urea nitrogen and erythrocyte glutathione peroxidase activity had decreased significantly, whereas plasma and erythrocyte protein-bound sulfhydryl groups had increased significantly. Furthermore, plasma glutathione and total antioxidant capacity were significantly greater after 2 months and increased further after 4 months of PBASS consumption. The results of next generation sequencing showed that PBASS consumption prompted significant decreases in observed bacterial species, their richness, and the abundance of Actinobacteria and Patescibacteria and increases in Bacteroidetes in feces. Our results suggest that texture-modified, plant-based snacks are useful nutrition support to benefit healthy ageing via the elevation of antioxidant ability and alteration of gut microbiota

Poria cocos Modulates Th1/Th2 Response and Attenuates Airway Inflammation in an Ovalbumin-Sensitized Mouse Allergic Asthma Model

Poria cocos, called fuling, is a famous tonic in traditional Chinese medicine that reportedly possesses various pharmacological properties, including anti-inflammation and immunomodulation. However, few studies have investigated the effects of P. cocos on allergic diseases, such as allergic asthma. Allergic asthma is caused primarily by Th2 immune response and characterized by airway inflammation. This study first demonstrated the anti-allergic and anti-asthmatic effects of P. cocos extract (Lipucan®). P. cocos extract distinctly exhibited reduced inflammatory cell infiltration in the peribronchial and peribronchiolar regions compared to the asthma group in the histological analysis of pulmonary tissue sections. Prolonged P. cocos extract administration significantly reduced eosinophil infiltration, PGE2 levels, total IgE, and OVA-specific IgE. Moreover, P. cocos extract markedly suppressed Th2 cytokines, IL-4, IL-5, and IL-10. On the other hand, P. cocos extract significantly elevated IL-2 secretion by Th1 immune response. In addition, P. cocos extract elevated the IFN-γ level at a lower dose. We also observed that P. cocos extract increased the activity of NK cells. Our results suggest that P. cocos extract remodels the intrinsic Th1/Th2 response to prevent or alleviate allergy-induced asthma or symptoms

Interleukin-27 and interleukin-12 augment activation of distinct cord blood natural killer cells responses via STAT3 pathways

Umbilical cord blood is rich in primitive natural killer (NK) cells, which are activated by interleukin (IL)-12. It was previously reported that a novel IL-12 family cytokine, IL-27 comprised of EBI3 and p28, was elevated in maternal serum during normal pregnancy. Thus, we compared the immune regulatory functions of IL-27 and IL-12 on mononuclear cells derived from cord blood and adult peripheral blood. Methods: After stimulation with IL-27, IL-12, and IL-27 combined with IL-12, the cytotoxicity against BJAB lymphoma cells by blood mononuclear cells was performed. Then immunofluorescence staining, reverse transcriptase-polymerase chain reaction and Western blotting were used to detect the effects of IL-27 and IL-12 in isolated NK cells. Results: IL-27, IL-12, and IL-27 combined with IL-12 enhanced the cytotoxicity of adult peripheral blood cells and cord blood cells, but the proliferation of distinct subpopulations of cells was not evident. Similar results were also obtained with purified cord blood NK cells. Interestingly, distinct from IL-12, IL-27 could induce aggregation and morphological changes of umbilical cord blood cells. Finally, IL-27 combined with IL-12 could stimulate increased IL-27 receptor (gp130 and WSX-1) transcripts in purified cord blood NK cells. However, the activation of signal transducer and activator of transcription 3 (STAT3) in NK cells was only detected in the presence of IL-27, but not IL-12 alone. Conclusion: From previous results, we summarize our current understanding of the augmentation of distinct regulation of NK cells by IL-27 and IL-12

Toll-like receptor 4 and myeloid differentiation factor 88 mRNA in NZB/W mesangial cells (lipopolysaccharide treatment)

<p><b>Copyright information:</b></p><p>Taken from "Mesangial cells of lupus-prone mice are sensitive to chemokine production"</p><p>http://arthritis-research.com/content/9/4/R67</p><p>Arthritis Research & Therapy 2007;9(4):R67-R67.</p><p>Published online 7 Jul 2007</p><p>PMCID:PMC2206365.</p><p></p> Growth-arrested (under 2% fetal bovine serum (FBS)) mesangial cells were incubated with 10 μg/ml lipopolysaccharide (LPS) for different periods of time, and then Toll-like receptor 4 (TLR-4) and myeloid differentiation factor 88 (MyD88) mRNA levels were measured by real-time PCR analysis. The experiment was performed in triplicate, and results are expressed as the mean ± standard error, = 6. The last time point without LPS stimulation (unstimulated) was presented as the negative control. *< 0.05, **< 0.01