The immediate effects of lavender-based essential oil inhalation on subsequent polysomnography in people with poor sleep quality.

BACKGROUND: Although aromatherapy is considered an adjuvant therapy to promote sleep quality, few objective sleep testing instruments can confirm the effects of aromatherapy on sleep physiology. The purpose of this study was to confirm and compare the immediate effects of a single lavender essential oil (SLEO) group to a complex lavender essential oil (CLEO) group by objective polysomnography (PSG) recordings. METHODS: Participants were randomly divided into the SLEO group and CLEO group in this single-blind trial to explore the sleep effect of essential oil aroma. All the participants completed the sleep-related questionnaires and underwent two consecutive nights of PSG recordings, who had one night without aromatherapy and one night with one of the two aromas randomly assigned to them. RESULTS: Total of 53 participants were recruited for this study, 25 participants were in the SLEO group, and 28 were in the CLEO group. Baseline characteristics and sleep-related questionnaires were similar in both groups. Both SLEO and CLEO extended the total sleep time (TST) (Δ = 43.42 and 23.75 minutes, respectively) and sleep period time (SPT) (Δ = 38.86 and 24.07 minutes, respectively). The SLEO group further improved sleep efficiency and increased the amounts of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and decreased spontaneous arousals. However, there was no significant difference in PSG parameters between the SLEO and CLEO groups. CONCLUSION: Both SLEO and CLEO extended TST and SPT, with no significant differences between these two groups. These results warrant practical applications and merit future studies (Clinical trial registration: ClinicalTrials.gov : NCT03933553).

Effects of oligo-fucoidan on the immune response, inflammatory status and pulmonary function in patients with asthma: a randomized, double-blind, placebo-controlled trial.

Asthma is a common disease occurring worldwide. The clinical treatment of asthma is constantly revised and updated; however, it is associated with side effects. Our previous in vitro and ex vivo studies found that oligo-fucoidan can improve allergic immune responses and reduce airway inflammation. The purpose of this clinical trial was to investigate the effects of oligo-fucoidan on the immune status, inflammatory response, and pulmonary function of patients with asthma. Twenty asthmatic patients were randomly divided into two groups: (1) control group: receiving regular asthma treatment and supplementation with placebo; (2) fucoidan group: receiving regular asthma treatment and supplementation with oligo-fucoidan. Pulmonary function tests, the "Asthma Control Questionnaire" survey, biochemical data, inflammatory factors, and immune cell subtypes were detected. During treatment, the levels of WBC (p = 0.038) and creatinine (p = 0.012 and p = 0.008 at 12th and 24th weeks) were significantly decreased in the fucoidan group. Lung function (FEV1/FVC pr) significantly increased in the fucoidan group (p = 0.046). Regarding the proportion of immune cells, the level of IFN+ and CD4+IFN+cells in the fucoidan group was significantly increased during the treatment period (P < 0.05), while the proportions of CD3+CD4+ cells (p = 0.048) and CD3+CD8+ cells (p = 0.009) in the fucoidan group were significantly decreased during the treatment period. Regarding cytokines, the level of interleukin-8 (IL-8) was also significantly reduced in the fucoidan group during the treatment period.

Relationship between serum 25 hydroxyvitamin D (25(OH)D) levels and mental health in shift female nurses.

The nurses work long hours and in various shifts, and often accompanied by depression, fatigue, and sleep disorders. Many studies have found that 25 hydroxyvitamin D (25(OH)D) is related to mental health. We aimed to investigate the relationship between depression, sleep problems, fatigue, and serum 25(OH)D levels in shift nurses. We recruited 34 day-shift, 30 evening-shift and 31 night-shift nurses. The Beck Depression Inventory II (BDI-II), Numerical Rating Scale and General Sleep Disturbance Scale to evaluate the levels of depression, sleep problems, fatigue. Blood samples (20 ml) were collected under a fasting state to determine basic biochemistry and inflammatory parameters. In central of Taiwan, approximately 96.1% of shift nurses had deficient (< 20 ng/ml) (45 females and 1 male) and inadequate (20-29 ng/ml) (39 females and 2 male) 25(OH)D levels. Approximately 84.2% of shift nurses experienced fatigue. In sleep disturbance, night-shift nurses experienced significantly more severe sleep disturbance than day-shift and evening-shift nurses. However, no significant correlation was observed between 25(OH)D levels and mental health when the 25(OH)D level was categorized. 25(OH)D deficiency, sleep disturbance, depression, and fatigue were common in shift female nurses, but it was not possible to demonstrate the impact of 25(OH)D deficiency on the mental health of shift nurses in Taiwan.

Hepatoprotective Effect of Antrodia cinnamomea Mycelium in Patients with Nonalcoholic Steatohepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) has become a prominent liver disease in contemporary society because of the changing dieting styles. Complicated syndromes often accompanied by obesity and diabetes makes no standard treatment for NASH. Therefore, we investigated the potential role of Antrodia cinnamomea mycelium (ACM) as nutraceutical supplementation in the treatment of NASH in this 6-month randomized, double-blind, placebo-controlled study. METHOD: 28 Participants were treated with three capsules per day containing either 420 mg of ACM or 420 mg of starch as a placebo. The participants were required to follow a predetermined regular visit to hospital every three months during the intervention period (6 months). During each study visit, subjects underwent anthropometric measurements and blood testing for biochemical analysis, immune function assay, inflammatory cytokines assay, and FibroMax test. RESULTS: The ACM supplemented group had a significant improvement in steatosis and decreased in the inflammatory marker of TNF-α after three and six months. NASH patients who received ACM showed a significant decrease in the SteatoTest mean value from 0.66 at baseline to 0.49 at 6 months (p < 0.029) and the ActiTest mean value decreased from 0.46 at baseline to 0.30 at 6 months (p < 0.029). CONCLUSION: This is the first clinical investigation that explores the hepatoprotective effect of A. cinnamomea mycelium in patients with NASH. No participants experienced any adverse events during the study, which suggested that ACM is a safe alternative treatment for NASH.

The Study of Correlation Between Serum Vitamin D3 Concentrations and HBV DNA Levels and Immune Response in Chronic Hepatitis Patients.

Chronic hepatitis B (CHB) is a common chronic disease. Previous studies have shown a link between 25-hydroxyvitamin D3 (vitamin D3) concentration and liver disease. Hepatitis B virus (HBV) infection has been attributed to the inappropriate functioning of cell-mediated immunity. However, the effects of vitamin D3, immune cell, and HBeAg status on HBV viral load in CHB patients are still unclear. We investigated the relationship between the serum concentration of vitamin D3, percentage of immune cells in peripheral blood, and the HBV viral load of CHB patients. Sixty CHB patients were recruited, and their blood samples were collected and analyzed. Vitamin D level was measured using a chemiluminescence assay. A level of 30 ng/mL or above was defined as a vitamin D3 sufficiency. We assigned vitamin D3 status as either normal (≥30 ng/mL), insufficient (20-30 ng/mL), or deficient (<20 ng/mL). T-lymphocyte and B-lymphocyte surface markers in peripheral blood were detected using flow cytometry. The factors associated with HBV viral load were analyzed using univariate and multivariate-adjusted models. The mean serum vitamin D3 concentration in the subjects was 20.9±5.6 ng/mL. Up to 88.3% of the patients were either deficient in or had insufficient vitamin D3. The gender, BMI, hepatitis B surface antigen levels, and ALT levels were significantly related to serum vitamin D3 levels. Serum vitamin D3 concentration, HBe status, HBs levels, ALT, and AST levels showed a statistically significant correlation with the HBV DNA levels. Serum vitamin D3 concentrations and hepatitis B surface antigen levels were strongly correlated with HBV DNA levels. Vitamin D3 levels were significantly associated with CD19 numbers (ß:-6.2, 95% CI: -10.5). In multivariate analysis, vitamin D3 levels in the deficient and insufficient groups, and the CD8, HBeAg, and WBC counts were significantly associated with HBV DNA levels. In the immune tolerance phase of HBeAg-negative chronic HBV infection, vitamin D3 may be a modulator of immune function via CD8, CD19, and HBV DNA.

The 25(OH)Vitamin D Status Affected the Effectiveness of Oligo Fucoidan in Patients with Chronic Hepatitis B Virus Infection with Immune Tolerance Phase.

Chronic hepatitis B virus (HBV) infection is a serious public health issue. Vitamin D is involved in various pathophysiological mechanisms as an immune modulator and the deficiency rate of vitamin D is prevalent in chronic liver disease. Fucoidan exerts anti-inflammatory, anticoagulant, antitumor, antimetastatic, and antiangiogenetic effects; however, its effect on the immune responses of HBV patients is unclear. This study investigated how 25(OH)Vitamin D status affected the effectiveness of oligo fucoidan in patients with HBV infection in the immune tolerance phase. Fifty-one patients received oligo fucoidan 4400 mg/day for 48 weeks. Flow cytometry was used to detect T lymphocyte markers (CD3+CD4+, CD3+CD8+, CD4+CD45RO+, CD8+CD45RO+). The levels of white blood cell (WBC), platelets (PLT), and albumin were decreased after 48 weeks of supplementation (p < 0.05). Percentages of CD3+CD8+ and CD8+CD45RO+ cells were decreased after 12 weeks of supplementation (p < 0.05). In patients with adequate vitamin D, HBV-DNA concentrations decreased and the proportion of CD4+CD45RO+ and CD8+CD45RO+ cells increased upon oligo fucoidan supplementation. The HBeAg status of one vitamin D-adequate patient changed from positive to negative at the 12th week of supplementation. The oligo fucoidan may regulate immune effects in patients with HBV infection, and the 25(OH)Vitamin D status might have affected the effectiveness of oligo fucoidan.

Oligo-fucoidan improved unbalance the Th1/Th2 and Treg/Th17 ratios in asthmatic patients: An ex vivo study.

An imbalance in the helper T cells (Th)1/Th2 and regulatory T cells (Tregs)/Th17 ratios is believed to play a key role in asthmatic inflammatory responses. Fucoidan reportedly reduces the production of inflammatory factors. Nutritional intervention is an important tool in decreasing the severity of asthmatic disease. This study aimed to investigate the beneficial roles of oligo-fucoidan in balancing the T cell subtype ratios and reducing airway inflammation ex vivo. Peripheral blood mononuclear cells (PBMCs) were collected from 30 asthmatic subjects and 15 healthy subjects. Harvested PBMCs were stimulated and treated with or without oligo-fucoidan (100 or 500 µg/ml) for 48 h. Cell surface and intracellular cytokine markers were examined by flow cytometry. The pro-inflammatory factors in plasma and culture supernatants were measured using ELISA kits. We found that oligo-fucoidan increases the proportion of Th1 and Treg cells, but did not affect the proportion of Th2 and Th17 cells. Oligo-fucoidan also increased the levels of interferon-γ and interleukin-10. Thus, we concluded that oligo-fucoidan might improve the imbalance in Th1/Th2 and Treg/Th17 ratios to reduce airway inflammation, which could be a potential adjuvant therapy for allergic asthma.

The declined levels of inflammatory cytokines related with weaning rate during period of septic patients using ventilators.

INTRODUCTION: Approximately 50% of patients with sepsis-induced acute lung injury and acute respiratory distress syndrome require mechanical ventilation. Patients with extended mechanical ventilator use routinely develop reinfections, which increases hospital stay, mortality, and health care cost. Some studies have pointed out inflammatory factors concentrations can affect ventilator weaning, but do not indicate changed inflammatory factors related to ventilator weaning during using ventilators. OBJECTIVES: This study aimed to investigate during period of septic patients using ventilators, the inflammatory cytokines concentrations related with weaning rate. METHODS: Blood was collected from 35 septic patients before and during ventilator use on days 1, 7, 14, and 21 (or weaning). RESULTS: 58.3% (N = 20) of septic patients with mechanical ventilators were weaned successfully within 21 days (ventilator weaned group, VW), 16.7% (N = 6) did not wean within 21 days (ventilator dependent group, VD), and 25% died (death group) in hospital. Before ventilator use, higher C-reactive protein (CRP), IL-6, and IL-8 levels were measured in the death group than in all other groups (P < .05). During ventilator use, CRP, IL-6, and IL-8 concentrations declined significantly in VW and VD patients (P < .05). In addition, IL-6 concentrations in the VW group were significantly lower than in the VD group at 14 and 21 days (P < .05). CONCLUSION: The factors of ventilators weaning successfully such as disease control, nutritional status, and so on. The declined levels of serum inflammatory cytokines, especially IL-6, improved inflammation status might be one factor of successfully weaning during septic patients on ventilators.

Zinc sulfate improved the unbalanced T cell profiles in Der p-allergic asthma: An ex vivo study.

INTRODUCTION: In the pathogenesis of asthma, an imbalance between helper T (Th) 1/Th2 and Th17/Treg cells is believed to play a key role in asthmatic inflammatory responses. Some studies indicated that zinc deficiency increases inflammatory factor production and worsens asthma. However, the effects of zinc on T cell profiles to reduce inflammatory response remain unclear. OBJECTIVES: We investigated the beneficial effects of zinc on isolated cell populations and cytokine levels from patients with asthma. METHODS: Thirty-six individuals Dermatophagoides pteronyssinus (Der p)-allergic and 31 healthy subjects were enrolled in the study, and peripheral blood mononuclear cells (PBMCs) were collected. Harvested PBMCs were stimulated with recombinant Der p antigen in the presence or absence of zinc sulfate (25 µM or 50 µM) for 48 h. Cell surface markers and intracellular cytokine levels were examined by flow cytometry. The pro-inflammatory factors in plasma and culture supernatants were measured by commercial enzyme-linked immunosorbent assay. RESULTS: Zinc sulfate dramatically reduced the proportions of Th2 and Th17 cells, but increased that of Th1 and Treg cells. Zinc sulfate also markedly reduced the levels of interleukin (IL)-4 and IL-17, but increased the levels of IFN-γ. CONCLUSIONS: Zinc ameliorates the imbalance in T cell profiles and could be a potential adjuvant therapy for Der p-induced allergic hypersensitivity.

The Changed Proportion of CD45RA+/CD45RO+ T Cells in Chronic Hepatitis C Patients During Pegylated Interferon-α with Ribavirin Therapy.

Infection with the hepatitis C virus (HCV) may progress toward chronic hepatitis, liver cirrhosis, and liver cancer. A therapy for patients with chronic HCV infection is the combination of pegylated interferon-α with ribavirin, which increases the rate of sustained virological response (SVR) to 56%. However, a practical biomarker to predict SVR is lacking. T cells expressing the CD45RA isoform are considered naive, and antigenic stimulation converts them to CD45RO+. CD45RO+ T cells exhibit immediate response and high lymphokine production, leading to the maintenance and upregulation of immune reactions. The aim of this study is to clarify the proportions of CD45RA+ and CD45RO+ T cells associated with rapid virological response and SVR. We collected blood samples from 32 HCV patients receiving the combined treatment. The samples were collected before, during 4th, 12th, and 24th therapy weeks, and 4th week posttherapy, and their T cell populations were analyzed using flow cytometry. Twenty-nine patients (90.6%) achieved SVR. There were significant declines in proportions of CD45RA+ cells during 4th, 12th, and 24th therapy weeks, and significant increases in proportions of CD45RO+ cells during 24th therapy week and 4th week posttherapy (P < 0.05). Patients undergoing hepatitis C therapy exhibited lowered CD45RA+ cell proportions and increased CD45RO+ cell proportions. This effect may be important in a patient's response to pegylated interferon-α with ribavirin therapy.

The Oligo Fucoidan Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation of Airway Smooth Muscle Cells.

In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs) is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has antiviral, antioxidant, antimicrobial, anticlotting, and anticancer properties; however, its effectiveness for asthma has not been elucidated thus far. Platelet-derived growth factor (PDGF)-treated primary ASMCs were cultured with or without oligo-fucoidan (100, 500, or 1000 µg/mL) to evaluate its effects on cell proliferation, cell cycle, apoptosis, and Akt, ERK1/2 signaling pathway. We found that PDGF (40 ng/mL) increased the proliferation of ASMCs by 2.5-fold after 48 h (p < 0.05). Oligo-fucoidan reduced the proliferation of PDGF-stimulated ASMCs by 75%-99% after 48 h (p < 0.05) and induced G1/G0 cell cycle arrest, but did not induce apoptosis. Further, oligo-fucoidan supplementation reduced PDGF-stimulated extracellular signal-regulated kinase (ERK1/2), Akt, and nuclear factor (NF)-κB phosphorylation. Taken together, oligo-fucoidan supplementation might reduce proliferation of PDGF-treated ASMCs through the suppression of ERK1/2 and Akt phosphorylation and NF-κB activation. The results provide basis for future animal experiments and human trials.

The plasma concentration of copper and prevalence of depression were positively correlated in shift nurses.

Several studies have reported the prevalence of depression in shift nurses to be 15%, and in some cases it may even be as high as 23%. Depression is a major cause of poor sleep quality and can impede efforts to overcome the chronic fatigue that commonly affects shift nurses. Adverse mental health issues have been confirmed in shift nurses, but few studies have investigated the underlying cause of poor mental health in different shift-nurse populations. Therefore, the aim of this study was to investigate the relationship of serum trace element levels to mental health and the tendency toward depression in shift nurses. We collected blood samples from 90 shift nurses (day, evening, and night shift) who worked in intensive care units and asked them to complete a general data questionnaire as well as the Chinese version of the Beck Depression Inventory, second edition. The night-shift nurses showed mild-to-moderate depression levels, which were significantly higher than those of the control group and other shift nurses. Night-shift nurses also had higher levels of plasma copper, ferritin, interleukin (IL)-6, and alanine aminotransferase (p < .05) than the control group and other nurses. Elevated concentrations of ferritin and IL-6 are considered important markers for the onset of depression. The results of this study suggest that plasma copper concentrations in nurses should be monitored.

The increased ratio of CD4+/CD8+ was positively correlated with inflammation in hepatitis C patients with metabolic syndrome.

BACKGROUND/AIMS: The incidence of metabolic syndrome (MS) in hepatitis C patients in Taiwan is not well known. Although the ratio of CD4(+)/CD8(+) T lymphocytes is considered to possibly affect the pathogenesis of hepatitis C, the effects of MS on CD4(+)/CD8(+) T lymphocytes remain unknown. The aims of this study to assess (1) the incidence of MS, (2) the inflammation status and fatty changes of liver, and (3) changes in their CD4(+)/CD8(+) T-lymphocyte ratio in patients with hepatitis C. METHODS: 60 hepatitis C patients were classified into MS or non-MS group. The terms of anthropometric data, MS components, and T-lymphocytes were assessed. RESULTS: The proportion of hepatitis C patients suffering from MS was 26.7% in this study. The CD4(+)/CD8(+) T-lymphocyte ratios were higher in patients with MS than non-MS group. Hepatitis C patients with MS also had higher levels of ferritin than non-MS. Moreover, the level of ferritin positively correlated with the severity of fatty liver. The CD4(+)/CD8(+) T-lymphocyte ratio is also positively correlated with ferritin level and the severity of fatty liver. CONCLUSIONS: Hepatitis C patients with MS had higher ratio of CD4(+)/CD8(+) T lymphocyte, which is associated with a high inflammatory response and a fatty change of liver.

Zinc sulfate inhibited inflammation of Der p2-induced airway smooth muscle cells by suppressing ERK1/2 and NF-κB phosphorylation.

Inflammation of airway smooth muscle cells (ASMCs) is believed to be important in causing airway hyperresponsiveness. However, zinc has been reported to be implicated in many kinds of cell inflammation. Little is known about the effect of zinc treatment on Der p2 (group II Dermatophagoides pteronyssinus)-induced inflammation from ASMCs. This study investigated effects and mechanisms of zinc in Der p2-treated ASMCs. Der p2-treated primary ASMCs were cultured with various concentrations of zinc sulfate (ZnSO4) 6 µM, 12 µM, 24 µM, and 96 µM. The proteins and mRNAs of cytokines in ASMCs were examined by ELISA and real-time PCR. Intracellular zinc was stained with Zinquin fluorescence. The cell signaling protein expression was detected by Western blot. Der p2 was used to induce interleukin (IL)-6, IL-8, IL-1, and monocyte chemotactic protein-1 production of ASMCs. However, we found that 24 µM ZnSO4 reduced these inflammatory mediators production of Der p2-treated primary ASMCs. Der p2-induced extracellular signal-regulated kinases (ERK) and nuclear factor-kappa B (NF-κB) phosphorylation were suppressed by supplementation of 24 µM ZnSO4. Zinc is an anti-inflammatory agent that reduces inflammation of Der p2-treated ASMCs through the suppression of the ERK and NF-κB pathway. The results may be helpful for the development of effective treatments.

The supplementation of zinc increased the apoptosis of airway smooth muscle cells by increasing p38 phosphorylation.

Proliferation of airway smooth muscle cells (ASMCs) is believed to play an important role in causing airway hyperresponsiveness (AHR). It has also been reported that platelet-derived growth factor (PDGF) can stimulate proliferation of ASMCs. We hypothesize that the concentration of zinc in the bodies of asthmatic patients may play a role in PDGF activity and therefore may be related to the variations in severity of airway inflammation and narrowing seen in asthmatic patients. We investigated the effects and mechanisms of zinc supplementation in PDGF-treated ASMCs. In this study, PDGF-treated primary ASMCs were cultured with 3, 12, 24, or 96 µM ZnSO4. We found that the highest concentration of ZnSO4 (96 µM) was cytotoxic for ASMCs. PDGF was used to induce ASMCs proliferation under different zinc concentrations. Neither 3 µM nor 12 µM ZnSO4 inhibited proliferation of PDGF-treated ASMCs, although 24 µM ZnSO4 caused treatment-induced apoptosis in PDGF-treated ASMCs. Supplementation with 24 µM ZnSO4 may therefore increase p38 activation and reduce Akt phosphorylation. Zinc supplementation may reduce proliferation of PDGF-treated ASMCs through the activation of p38 mitogen-activated protein kinase (MAP kinase) and suppression of Akt phosphorylation, which both drive the induction of cellular apoptosis, subsequently reducing the proliferation of ASMCs.

The extract of Cordyceps sinensis inhibited airway inflammation by blocking NF-κB activity.

Aiming the extract of Cordyceps sinensis significantly inhibits airway inflammation, airway hyperresponsiveness, and the infiltration of eosinophils in the airway of rats and may be related to the modulation of T helper (Th)1 and Th2 cells functions. The mechanisms of C. sinensis involved in modulation of suppression inflammation are not yet determined. In this study, the mechanism involved in the extract of C. sinensis-C.S.3-modulated suppression of inflammation was investigated in vivo and in vitro systems. The results showed that C.S.3 reduced airway inflammation in ovalbumin-induced allergic mice. Furthermore, we found C.S.3 could decrease extracellular signal-regulated kinase 1/2 signaling pathway to suppress activity of nuclear factor-κB in lung cells and cultured airway smooth muscle cells. Conclusion C.S.3 may provide clinical applications for asthma in the future.

Hyperbaric oxygen-stimulated proliferation and growth of osteoblasts may be mediated through the FGF-2/MEK/ERK 1/2/NF-κB and PKC/JNK pathways.

We investigated whether the hyperbaric oxygen (O2) could promote the proliferation of growth-arrested osteoblasts in vitro and the mechanisms involved in this process. Osteoblasts were exposed to different combinations of saturation and pressure of O2 and evaluated at 3 and 7 days. Control cells were cultured under ambient O2 and normal pressure [1 atmosphere (ATA)]; high-pressure group cells were treated with high pressure (2.5 ATA) twice daily; high-O2 group cells were treated with a high concentration O2 (50% O2) twice daily; and high pressure plus high-O2 group cells were treated with high pressure (2.5 ATA) and a high concentration O2 (50% O2) twice daily. Hyperbaric O2 significantly promoted osteoblast proliferation and cell cycle progression after 3 days of treatment. Hyperbaric O2 treatment stimulated significantly increased mRNA expression of fibroblast growth factor (FGF)-2 as well as protein expression levels of Akt, p70(S6K), phosphorylated ERK, nuclear factor (NF)-κB, protein kinase C (PKC)α, and phosphorylated c-Jun N-terminal kinase (JNK). Our findings indicate that high pressure and high O2 saturation stimulates growth-arrested osteoblasts to proliferate. These findings suggest that the proliferative effects of hyperbaric O2 on osteoblasts may contribute to the recruitment of osteoblasts at the fracture site. The FGF-2/MEK/ERK 1/2/Akt/p70(S6K)/NF-κB and PKC/JNK pathways may be involved in mediating this process.

Induction of IL-10+ CD4+ CD25+ regulatory T cells with decreased NF-κB expression during immunotherapy.

MyD88 is a major toll-like receptor (TLR) adaptor to activate NF-κB, which acts as a mater switch for allergic inflammation disease. Sterile hust dust extracts have been reported with TLR-dependent immunostimulatory activities. The aim of this study was to evaluate whether Dermatophagoides pteronyssinus (Der p) immunotherapy may increase IL-10+ CD4+ CD25+ T cells with modulating MyD88 signaling proteins, to decrease NF-κB expression. Peripheral blood mononuclear cells were isolated from patients before and after 1 yr of Der p immunotherapy, and also from matched control subjects. After 2 days of Der p-2 stimulation, intracellular IL-10 and Foxp3 expression of CD4(+) CD25(+) T cells were measured by flow-cytometry. The expression of IL-1 receptor-associated kinase (IRAK)-1 in cytoplasm and IFN-regulator factor-3 (IRF-3) with NF-κB/p65 in nuclei was determined by Western-blot analysis. Patients undergoing immunotherapy produced more soluble CD14, IL-10, and TGF-ß that correlated with FEV(1) improvement (p < 0.05). In the immunotherapy group, the number of Foxp3+ CD4+ Treg cells increased more than the baseline status (25.06 ± 4.19 vs. 16.08 ± 3.54, p < 0.05). Additionally, increased IL-10 production with decreased IRAK-1 and NF-κB/p65 nuclear translocation was observed in sorted-purified Treg cells. IL-10(+) CD4(+) CD25(+) Treg cells may respond to Der p-2 and down-regulate NF-κB/p65 expression to maintain immune tolerance during immunotherapy.

Der p2 activates airway smooth muscle cells in a TLR2/MyD88-dependent manner to induce an inflammatory response.

Der p2 is a major allergen from Dermatophagoides pteronyssinus, the main species of house dust mite and a major inducer of asthma, inducing harmful respiratory inflammatory responses by activating cells in the respiratory tract, leading to an unstable status. We hypothesize that Der p2 may induce local inflammatory responses by directly affecting airway smooth muscle (ASM) cells. In this study, we demonstrated that Der p2 raised nuclear factor-kappa B (NF-kappaB) and extracellular signal-regulated kinase (ERK) 1/2 activation and induced a high level of proinflammatory cytokines expression in primary cultured ASM cells. Der p2 activated the MyD88 signaling pathway through toll-like receptor (TLR) 2, not through TLR4. Notably, Der p2 stimulated ASM cells to increase phosphorylation of ERK1/2 and expression of c-Fos, which were also important in the T helper type 2 (Th2) immune response. These results suggest that Der p2 induces asthma through the MyD88 signaling pathway in respiratory tissue.

Blocking of Akt/NF-kappaB signaling by pentoxifylline inhibits platelet-derived growth factor-stimulated proliferation in Brown Norway rat airway smooth muscle cells.

The proliferation of airway smooth muscle cells (ASMC) can cause airway hyperresponsiveness (AHR). It has been reported that platelet-derived growth factor (PDGF) can stimulate the proliferation of ASMC through phosphatidylinositol 3-kinase (PI3 K) signaling pathway, which can activate Akt protein. Activated-Akt can activate downstream signal protein [p70S6 K, nuclear factor (NF)-kappaB, and extracellular signal regulated kinase (ERK)], increasing the cyclin D1 level and suppressing the transcription of p27Kip1 to enable cell cycle entry. This investigation demonstrated that pentoxifylline (PTX) inhibited the PDGF-stimulated proliferation of ASMC by suppressing activation of the Akt/NF-kappaB pathway. ASMC were treated with PTX for 48 h, which attenuated the PDGF-stimulated proliferation of ASMC. PTX and wortmannin, a PI3 K inhibitor, not only inhibited the PDGF-activated phosphorylation of Akt but also suppressed p70S6 K expression and IkappaBalpha degradation, inhibiting nuclear translocation and the DNA binding activity of NF-kappaB. However, PTX did not influence the phosphorylation of ERK1/2. The suppression of p70S6 K by rapamycin did not influence cyclin D1 expression in PDGF-stimulated cells. These data reveal that the down-regulation of the Akt/NF-kappaB signaling pathway by PTX inhibited the proliferation of ASMC. PTX may provide information on the pathogenesis of asthma.