Mushroom product induces a Th1 response and may possess a potential effect in regulating immune r... more Mushroom product induces a Th1 response and may possess a potential effect in regulating immune responses. Ganoderma lucidum, an oriental medicinal mushroom, has been widely used in Asia to promote health and longevity. LZ-8 is a protein derived from the fungus G. lucidum and has immunomodulatory capacities. In this study, we investigated the immune modulatory effects of rLZ-8 on human monocyte-derived DCs. Treatment of DC with rLZ-8 resulted in the enhanced cell-surface expression of CD80, CD86, CD83, and HLA-DR, as well as the enhanced production of IL-12 p40, IL-10, and IL-23, and the capacity for endocytosis was suppressed in DCs. In addition, treatment of DCs with rLZ-8 resulted in an enhanced, naïve T cell-stimulatory capacity and increased, naïve T cell secretion of IFN-γ and IL-10. Neutralization with antibodies against TLR4 inhibited the rLZ-8-induced production of IL-12 p40 and IL-10 in DCs. rLZ-8 can stimulate TLR4 or TLR4/MD2-transfected HEK293 cells to produce IL-8. The...
Sleep disturbance is common in children with atopic dermatitis (AD), but effective clinical manag... more Sleep disturbance is common in children with atopic dermatitis (AD), but effective clinical management for this problem is lacking. Reduced levels of nocturnal melatonin were found to be associated with sleep disturbance and increased disease severity in children with AD. Melatonin also has sleep-inducing and anti-inflammatory properties and therefore might be useful for the management of AD. To evaluate the effectiveness of melatonin supplementation for improving the sleep disturbance and severity of disease in children with AD. This randomized clinical trial used a double-blind, placebo-controlled crossover design to study 73 children and adolescents aged 1 to 18 years with physician-diagnosed AD involving at least 5% of the total body surface area. The study was conducted at the pediatric department of a large tertiary care hospital in Taiwan from August 1, 2012, through January 31, 2013. Forty-eight children were randomized 1:1 to melatonin or placebo treatment, and 38 of these ...
Mycobacterium avium complex-induced lung disease (MAC-LD) becomes important due to its increasing... more Mycobacterium avium complex-induced lung disease (MAC-LD) becomes important due to its increasing prevalence. Attenuated cellular immunity associated with programmed cell death (PD)-1 may play a pathophysiological role in MAC-LD but lacks of investigation. We enrolled 80 participants in this prospective study, including 50 with MAC-LD and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs), lymphocytes and monocyte-derived macrophages were used for MAC antigen stimulation. Patients with MAC-LD had lower tumor necrosis factor-α and interferon-γ responses compared to the healthy controls in PBMC stimulation assays with MAC bacilli. These responses improved after MAC treatment. The PD-1 and PD ligand expressions and apoptosis were higher in the lymphocytes of the patients with MAC-LD compared to the controls. Both PD-1 and apoptosis on T lymphocytes were significantly increased in the patients with MAC-LD, either by direct MAC stimulation or by MAC-primed macrophage activat...
The role of B cells in the development of CD4(+) regulatory T cells has been emphasized recently.... more The role of B cells in the development of CD4(+) regulatory T cells has been emphasized recently. Our previous studies have demonstrated that the antigen-presenting splenic B cells converted naïve CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(-) T cells without additional cytokines or chemicals with regulatory activity and that referred to as Treg-of-B cells. The present study further showed that Treg-of-B cells increased the IL-10-producing population, and the expression of c-Maf, inducible T-cell co-stimulator (ICOS) as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) after repeated stimulation of B cells in a cell-cell contact-dependent manner. Long-term cultured Treg-of-B cells exerted IL-10 and CTLA4-mediated antigen-specific suppressive activity; moreover, the single antigen-specific Treg-of-B cells inhibited in a non-antigen-specific fashion. In conclusion, these results suggest that repeated stimulation of B cells induced IL-10-producing CD4(+)Foxp3(-) regulatory ...
Airway epithelium defends the invasion from microorganisms and regulates immune responses in alle... more Airway epithelium defends the invasion from microorganisms and regulates immune responses in allergic asthma. Thymic stromal lymphopoietin (TSLP) from inflamed epithelium promotes maturation of dendritic cells (DCs) to prime Th2 responses via CCL17, which induces chemotaxis of CD4(+) T cells to mediate inflammation. However, few studies have investigated the regulation of epithelial CCL17. In this study, we used shRNA against TSLP to clarify the role of TSLP in the airway inflammation and whether TSLP affects the airway inflammation via epithelial CCL17. Specific shTSLP was delivered by lentivirus and selected by the knockdown efficiency. Allergic mice were intratracheally pretreated with the lentivirus and followed by intranasal ovalbumin (OVA) challenges. The sera antibody levels, airway inflammation, airway hyper-responsiveness (AHR), cytokine levels in bronchoalveolar lavage fluids, and CCL17 expressions in lungs were determined. In vivo, TSLP attenuation reduced the AHR, decrea...
Regulatory T cells have a crucial role in health and disease because of their immune regulation f... more Regulatory T cells have a crucial role in health and disease because of their immune regulation function. However, the anatomic sites where regulatory T cells exert optimal immune regulation are open to debate. In our current study with the use of a shear-stress flow assay, we found that regulatory T cells exhibited significantly decreased adhesion to either activated endothelial monolayer or intercellular adhesion molecule 1 or E-selectin-coated surfaces compared with activated effector T cells. The less transmigration capacity of the regulatory T cells prompted our speculation of preferential lymph node localization for the regulatory T cells that endowed these cells with immune regulation function in the most efficient manner. To test this hypothesis, the role of lymph node localization in regulatory T cell-mediated immune suppression was evaluated with a footpad inflammation model. We found that adoptively transferred regulatory T cells inhibited the development of footpad infla...
Evidence-Based Complementary and Alternative Medicine, 2015
This study was to investigate antiallergic effects of triterpenoids (Gt-TRE) and polysaccharide (... more This study was to investigate antiallergic effects of triterpenoids (Gt-TRE) and polysaccharide (Gt-PS) extracts fromGanoderma tsugae, using mast cell line RBL-2H3, T cell line EL4, primary T cells, and transfected RAW264.7 macrophage cells. The results showed that histamine secreted from activated RBL-2H3 mast cells was significantly suppressed by Gt-TRE but not Gt-PS. Interleukin- (IL-) 4 secreted from activated EL4 cells was significantly suppressed by Gt-TRE but not Gt-PS. Further primary CD4+T cells cultures also confirmed that Gt-TRE (5~50 µg/mL) significantly suppressed Th2 cytokines IL-4 and IL-5 secretions but had no effect on Th1 cytokines IL-2 and interferon (IFN)-γ. Gt-PS did not affect IL-4 and IL-5 secretions until higher doses (400, 500 µg/mL) and significantly suppressed IFNγsecretions but enhanced IL-2 at these high doses. The reporter gene assay indicated that Gt-TRE inhibited but Gt-PS enhanced the transcriptional activity of NF-κB in activated transfected RAW264....
Mushroom product induces a Th1 response and may possess a potential effect in regulating immune r... more Mushroom product induces a Th1 response and may possess a potential effect in regulating immune responses. Ganoderma lucidum, an oriental medicinal mushroom, has been widely used in Asia to promote health and longevity. LZ-8 is a protein derived from the fungus G. lucidum and has immunomodulatory capacities. In this study, we investigated the immune modulatory effects of rLZ-8 on human monocyte-derived DCs. Treatment of DC with rLZ-8 resulted in the enhanced cell-surface expression of CD80, CD86, CD83, and HLA-DR, as well as the enhanced production of IL-12 p40, IL-10, and IL-23, and the capacity for endocytosis was suppressed in DCs. In addition, treatment of DCs with rLZ-8 resulted in an enhanced, naïve T cell-stimulatory capacity and increased, naïve T cell secretion of IFN-γ and IL-10. Neutralization with antibodies against TLR4 inhibited the rLZ-8-induced production of IL-12 p40 and IL-10 in DCs. rLZ-8 can stimulate TLR4 or TLR4/MD2-transfected HEK293 cells to produce IL-8. The...
Sleep disturbance is common in children with atopic dermatitis (AD), but effective clinical manag... more Sleep disturbance is common in children with atopic dermatitis (AD), but effective clinical management for this problem is lacking. Reduced levels of nocturnal melatonin were found to be associated with sleep disturbance and increased disease severity in children with AD. Melatonin also has sleep-inducing and anti-inflammatory properties and therefore might be useful for the management of AD. To evaluate the effectiveness of melatonin supplementation for improving the sleep disturbance and severity of disease in children with AD. This randomized clinical trial used a double-blind, placebo-controlled crossover design to study 73 children and adolescents aged 1 to 18 years with physician-diagnosed AD involving at least 5% of the total body surface area. The study was conducted at the pediatric department of a large tertiary care hospital in Taiwan from August 1, 2012, through January 31, 2013. Forty-eight children were randomized 1:1 to melatonin or placebo treatment, and 38 of these ...
Mycobacterium avium complex-induced lung disease (MAC-LD) becomes important due to its increasing... more Mycobacterium avium complex-induced lung disease (MAC-LD) becomes important due to its increasing prevalence. Attenuated cellular immunity associated with programmed cell death (PD)-1 may play a pathophysiological role in MAC-LD but lacks of investigation. We enrolled 80 participants in this prospective study, including 50 with MAC-LD and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs), lymphocytes and monocyte-derived macrophages were used for MAC antigen stimulation. Patients with MAC-LD had lower tumor necrosis factor-α and interferon-γ responses compared to the healthy controls in PBMC stimulation assays with MAC bacilli. These responses improved after MAC treatment. The PD-1 and PD ligand expressions and apoptosis were higher in the lymphocytes of the patients with MAC-LD compared to the controls. Both PD-1 and apoptosis on T lymphocytes were significantly increased in the patients with MAC-LD, either by direct MAC stimulation or by MAC-primed macrophage activat...
The role of B cells in the development of CD4(+) regulatory T cells has been emphasized recently.... more The role of B cells in the development of CD4(+) regulatory T cells has been emphasized recently. Our previous studies have demonstrated that the antigen-presenting splenic B cells converted naïve CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(-) T cells without additional cytokines or chemicals with regulatory activity and that referred to as Treg-of-B cells. The present study further showed that Treg-of-B cells increased the IL-10-producing population, and the expression of c-Maf, inducible T-cell co-stimulator (ICOS) as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) after repeated stimulation of B cells in a cell-cell contact-dependent manner. Long-term cultured Treg-of-B cells exerted IL-10 and CTLA4-mediated antigen-specific suppressive activity; moreover, the single antigen-specific Treg-of-B cells inhibited in a non-antigen-specific fashion. In conclusion, these results suggest that repeated stimulation of B cells induced IL-10-producing CD4(+)Foxp3(-) regulatory ...
Airway epithelium defends the invasion from microorganisms and regulates immune responses in alle... more Airway epithelium defends the invasion from microorganisms and regulates immune responses in allergic asthma. Thymic stromal lymphopoietin (TSLP) from inflamed epithelium promotes maturation of dendritic cells (DCs) to prime Th2 responses via CCL17, which induces chemotaxis of CD4(+) T cells to mediate inflammation. However, few studies have investigated the regulation of epithelial CCL17. In this study, we used shRNA against TSLP to clarify the role of TSLP in the airway inflammation and whether TSLP affects the airway inflammation via epithelial CCL17. Specific shTSLP was delivered by lentivirus and selected by the knockdown efficiency. Allergic mice were intratracheally pretreated with the lentivirus and followed by intranasal ovalbumin (OVA) challenges. The sera antibody levels, airway inflammation, airway hyper-responsiveness (AHR), cytokine levels in bronchoalveolar lavage fluids, and CCL17 expressions in lungs were determined. In vivo, TSLP attenuation reduced the AHR, decrea...
Regulatory T cells have a crucial role in health and disease because of their immune regulation f... more Regulatory T cells have a crucial role in health and disease because of their immune regulation function. However, the anatomic sites where regulatory T cells exert optimal immune regulation are open to debate. In our current study with the use of a shear-stress flow assay, we found that regulatory T cells exhibited significantly decreased adhesion to either activated endothelial monolayer or intercellular adhesion molecule 1 or E-selectin-coated surfaces compared with activated effector T cells. The less transmigration capacity of the regulatory T cells prompted our speculation of preferential lymph node localization for the regulatory T cells that endowed these cells with immune regulation function in the most efficient manner. To test this hypothesis, the role of lymph node localization in regulatory T cell-mediated immune suppression was evaluated with a footpad inflammation model. We found that adoptively transferred regulatory T cells inhibited the development of footpad infla...
Evidence-Based Complementary and Alternative Medicine, 2015
This study was to investigate antiallergic effects of triterpenoids (Gt-TRE) and polysaccharide (... more This study was to investigate antiallergic effects of triterpenoids (Gt-TRE) and polysaccharide (Gt-PS) extracts fromGanoderma tsugae, using mast cell line RBL-2H3, T cell line EL4, primary T cells, and transfected RAW264.7 macrophage cells. The results showed that histamine secreted from activated RBL-2H3 mast cells was significantly suppressed by Gt-TRE but not Gt-PS. Interleukin- (IL-) 4 secreted from activated EL4 cells was significantly suppressed by Gt-TRE but not Gt-PS. Further primary CD4+T cells cultures also confirmed that Gt-TRE (5~50 µg/mL) significantly suppressed Th2 cytokines IL-4 and IL-5 secretions but had no effect on Th1 cytokines IL-2 and interferon (IFN)-γ. Gt-PS did not affect IL-4 and IL-5 secretions until higher doses (400, 500 µg/mL) and significantly suppressed IFNγsecretions but enhanced IL-2 at these high doses. The reporter gene assay indicated that Gt-TRE inhibited but Gt-PS enhanced the transcriptional activity of NF-κB in activated transfected RAW264....
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