Physical Properties and the Reconstruction of Unstable Decahedral Silver Nanoparticles Synthesized Using Plasmon-Mediated Photochemical Process.

Plasmon-mediated shape transformation from quasi-spherical silver nanoparticles (AgNPs) to silver nanoprisms (AgNPrs) and decahedral silver nanoparticles (D-AgNPs) under irradiation of blue LEDs (λ = 456 ± 12 nm, 80 mW/cm2) was studied at temperatures ranging between 60, 40, 30, 20, 10, and 0 °C. It was found that reaction temperature affected transformation rates and influenced the morphology distribution of final products. The major products synthesized at temperatures between 60 °C and 0 °C were AgNPrs and D-AgNPs, respectively. The D-AgNPs synthesized at such low temperatures are unstable and become blunt when light irradiation is removed after the photochemical synthesis. These blunt nanoparticles with pentagonal multiple-twinned structures can be further used as the seeds to reconstruct complete D-AgNPs after irradiating blue LEDs at various bath temperatures. Our results showed that these rebuilt D-AgNPs are much more stable when at higher bath temperatures. Furthermore, the rebuilt D-AgNPs (edge lengths ~41 nm) can grow into larger D-AgNPs (edge lengths ~53 nm) after the irradiation of green LEDs. Surface-enhanced Raman spectra of CV in AgNP colloids showed that D-AgNP colloids have better SERS enhancements factors than AgNPrs.

Functional interaction of common allergens and a C-type lectin receptor, dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), on human dendritic cells.

Fucosylated glycans on pathogens are known to shape the immune response through their interaction with pattern recognition receptors, such as C-type lectin receptors (CLRs), on dendritic cells (DCs). Similar fucosylated structures are also commonly found in a variety of allergens, but their functional significance remains unclear. To test a hypothesis that allergen-associated glycans serve as the molecular patterns in functional interaction with CLRs, an enzyme-linked immunosorbent assay-based binding assay was performed to determine the binding activity of purified allergens and allergen extracts. THP-1 cells and monocyte-derived DCs (MDDCs) were investigated as a model for testing the functional effects of allergen-CLR interaction using enzyme-linked immunosorbent assay, Western blotting, and flow cytometry. Significant and saturable bindings of allergens and allergen extracts with variable binding activities to DC-specific ICAM3-grabbing non-integrin (DC-SIGN) and its related receptor, L-SIGN, were found. These include bovine serum albumin coupled with a common glycoform (fucosylated glycan lacking the alpha1,3-linked mannose) of allergens and a panel of purified allergens, including BG60 (Cyn dBG-60; Bermuda grass pollen) and Der p2 (house dust mite). The binding activity was calcium-dependent and inhibitable by fucose and Lewis-x trisaccharides (Le(x)). In THP-1 cells and human MDDCs, BG60-DC-SIGN interaction led to the activation of Raf-1 and ERK kinases and the induction of tumor necrosis factor-alpha expression. This effect could be blocked, in part, by Raf-1 inhibitor or anti-DC-SIGN antibodies and was significantly reduced in cells with DC-SIGN knockdown. These results suggest that allergens are able to interact with DC-SIGN and induce tumor necrosis factor-alpha expression in MDDCs via, in part, Raf-1 signaling pathways.

Inhibitory effects of albuterol and fenoterol on RANTES and IP-10 expression in bronchial epithelial cells.

Short-acting ß2-adrenoreceptor agonist (SABA) is the major asthma reliever as indicated in the GINA guidelines. Regulated on activation, normal T expressed and secreted (RANTES) is a chemokine that attracts eosinophils, mast cells, and basophils toward site of allergic inflammation. Interferon γ-inducible protein (IP)-10 is a Th1-related chemokine that is also important in asthmatic inflammation and also involved in our immune defense against pathogens. Bronchial epithelial cells are first-line barrier against invasive pathogen and also have immunomodulatory function. However, whether albuterol and fenoterol (two SABAs) have modulatory effects on RANTES and IP-10 expression in bronchial epithelial cells is unknown. The human bronchial epithelial cell lines, BEAS-2B cells, were pre-treated with different concentrations of albuterol, fenoterol or dibutyryl-cAMP (a cyclic AMP analog) before polyinosinic-polycytidylic acid (poly I:C) stimulation. In some condition, BEAS-2B cells were pre-treated with ICI-118551, a selective ß2-adrenoreceptor antagonist, 30 min before albuterol or fenoterol treatment. The levels of RANTES and IP-10 were measured by ELISA. Intracellular signaling was investigated using cAMP assay, mitogen-activated protein kinase (MAPK) inhibitor, nuclear factor (NF)-κB inhibitor, and western blot. Albuterol and fenoterol suppressed poly I:C-induced RANTES and IP-10 expression of BEAS-2B cells. ICI-118551 could partly reverse the suppressive effects of albuterol and fenoterol on RANTES and IP-10 expression. Albuterol and fenoterol increased intracellular cAMP levels. Dibutyryl-cAMP conferred the similar effects of albuterol and fenoterol. Western blot revealed that albuterol suppressed p-ERK, p-JNK and pp38, and also their associated kinase expression. Albuterol had no effect on pp65 expression. Albuterol and fenoterol could suppress poly I:C-induced RANTES and IP-10 expression in human bronchial epithelial cells via at least partly the ß2-adrenoreceptor-cAMP and the MAPK pathways, implicating that albuterol and fenoterol could exert anti-inflammatory effect and benefit asthmatic patients by suppressing RANTES and IP-10 expression. However, these suppressive effects of albuterol and fenoterol may inhibit the defense against viral infection.

Prostaglandin I(2) analogues suppress TNF-α expression in human monocytes via mitogen-activated protein kinase pathway.

OBJECTIVE AND DESIGN: Although treatment for asthma control has improved a lot recently, refractory asthma is still a challenge for clinicians. Evidence revealed that anti-tumor necrosis factor (TNF)-α therapy may have potential in treating refractory asthma. Recently in an animal model, prostaglandin I(2) (PGI(2)) analogues can suppress the cardinal feature of asthma. However, whether PGI(2) analogues can regulate TNF-α expression in monocytes and the mechanism is not well-known. MATERIALS AND METHODS: The human monocytes were pretreated with beraprost, iloprost and treprostinil, three PGI(2) analogues, before stimulation with lipopolysaccharide (LPS). TNF-α concentration of the cell supernatants was measured by ELISA. Intracellular signaling was investigated by Western blot. RESULTS: PGI(2) analogues suppressed LPS-induced TNF-α expression in THP-1 cells. CAY10449, an I prostanoid receptor antagonist, could reverse these effects. Beraprost increased intracellular cAMP level in THP1 cells. Forskolin, an adenylyl cyclase activator, could confer similar effect. LPS-induced TNF-α expression in THP-1 cells could be reversed by mitogen-activator protein kinase (MAPK)-p38, extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors. Western blot revealed that beraprost suppressed MAPK phospho-p38, phosphor-JNK and phosphor-ERK expression. CONCLUSION: PGI(2) analogues suppressed LPS-induced TNF-α expression in THP-1 cells via the IP receptor-cAMP and the MAPK pathways. PGI(2) analogues may have potentiality to treat asthma.

Probiotics and allergy in children--an update review.

The hygiene hypothesis suggests that the increased prevalence of allergic diseases has resulted from a relative lack of microbial stimuli during infancy and early childhood. Children with atopic diseases have different commensal bacterial groups in the gut compared to non-atopic children, and differences are also found between countries with high and low incidence of atopic diseases. Probiotics are defined as live microorganisms that provide benefits to the health of a host by altering the host's microflora when they are administered in adequate amounts. They are being investigated for possible roles in managing allergic diseases. To date, the evidence that probiotics can be used to treat or prevent allergic diseases of children remains controversial. We reviewed recent randomized, double-blinded, placebo-controlled clinical trials using probiotics for allergic diseases of children and evaluated their clinical efficacy, possible mechanisms, dosage, and safety for managing allergic diseases of children. The current data are insufficient to strongly recommend probiotics as a standard treatment or preventative measure for pediatric allergic disease. More studies are needed to standardize study designs, bacterial strains, dosages, and durations for different allergic diseases of children.

The effects of NOS1 gene on asthma and total IgE levels in Taiwanese children, and the interactions with environmental factors.

Asthma is a complex disorder, which is known to be affected by interactions between genetic and environmental factors. The aim of this study was to investigate the three microsatellite polymorphisms of GT repeats in intron 2, AAT repeats in intron 20, and CA repeats in exon 29 of the NOS1 gene in 155 asthmatic children and 301 control children, and the interaction with environmental factors in southern Taiwan. Total serum IgE, phadiatop test and genetic polymorphisms were measured. The genotype frequency of 14/14-AAT repeats of the NOS1 gene was significantly higher in the asthmatic group (p = 0.01). Total IgE concentrations were higher in asthmatic children (p = 0.015) carrying the NOS1 14/14-AAT genotype than in subjects with other polymorphisms. The gene and environmental interaction effects were 3.83-fold, 6.86-fold, and 8.04-fold (all corrected p-values <0.001) between subjects carrying at least one NOS1 14-AAT allele and exposure to cockroaches, high levels of total IgE, and positive response against the phadiatop test in asthmatic children. The findings of this study provide strong evidence that NOS1 gene with 14-AAT tandem repeats has a significant effect in asthmatic children. Environmental factors and atopic status will enhance the asthmatic risk for children who carry NOS1 susceptible allele.

Suppressive effects of formoterol and salmeterol on eotaxin-1 in bronchial epithelial cells.

Eotaxin-1 (CCL11), an eosinophil-specific C-C chemokine, is a potent chemoattractant for mobilization of eosinophils into airways after allergic stimulation. Eotaxin-1 recruits eosinophils into inflammatory sites, and may play a role in the pathogenesis of asthma. Formoterol and salmeterol are two inhaled long acting beta(2) adrenoceptor agonists (LABAs), widely used for the local treatment of asthma. However, little is known about their effects on the eotaxin-1 expression of bronchial epithelial cells. BEAS-2B cells were stimulated by adding IL-4 with or without 2 h pre-treatment of formoterol or salmeterol. The protein and mRNA expression of eotaxin-1 were measured by ELISA assay and real-time PCR, respectively. Effects of formoterol and salmeterol on nuclear and cytosolic pSTAT-6 expression were evaluated by Western blot and immunofluorescence study. Formoterol and salmeterol (10(-7)-10(-10) m) significantly down-regulated IL-4- induced eotaxin-1 expression in BEAS-2B cells. A specific beta(2) adrenoceptor antagonist (ICI 118,551) reversed their suppression of eotaxin-1 production. Forskolin, an cAMP activator, could also suppress the expression of eotaxin-1 by IL-4 in a dose dependent manner (10(-7)-10(-10 )m). The western blot and immunofluorescence studies demonstrated that formoterol 10(-7 )m suppressed the nuclear expression of pSTAT-6. Formoterol and salmeterol, two inhaled long-acting beta(2) agonists, down-regulated IL-4- induced eotaxin-1 expression in BEAS-2B cells. The effect was mediated via the beta(2) adrenoceptor, and cAMP. Formoterol significantly down-regulated pSTAT6 at higher concentration, and further turned off the IL-4 signaling pathway.

Effects of all-trans retinoic acid on Th1- and Th2-related chemokines production in monocytes.

Low vitamin C and reduced alpha-carotene intake are associated with increased asthma risk in children. In addition, mean serum vitamin A concentrations are significantly lower in asthmatic children than in controls. All-trans retinoic acid (ATRA) is a derivative of vitamin A. Macrophage-derived chemokine (MDC) is a T helper cell-type 2 (Th2)-related chemokine involved in the recruitment of Th2 cells toward inflammatory sites. On the other hand, Th1-related chemokine, interferon-inducible protein 10 (IP-10)/CXCL10 is also important in allergic inflammation. Both Th1- and Th2-related chemokines play an important role in allergic asthma. To survey whether ATRA and ascorbic acid effect Th1- and Th2-related chemokine expression in monocytes. To test this, THP-1 cells were pre-treated with ATRA or ascorbic acid and stimulated by lipopolysaccharide (LPS) or poly I:C. Supernatants were measured for Th2-related (MDC) and Th1-related (IP-10) chemokine concentrations by ELISA. The effects of ATRA on mitogen-activated protein kinase (MAPK) and NFkb were evaluated with Western blotting. After stimulation, ATRA significantly down-regulated MDC and IP-10 in a dose-dependent manner. Similarly, ascorbic acid reduced the LPS-induced changes in MDC but only with a high dose. However, asorbic acid had no effect on IP-10 changes either induced by LPS or poly I:C. RT-PCR showed ATRA inhibited IP-10 expression through decreasing the level of transcription. Furthermore, ATRA suppressed the expression of LPS-stimulated c-Raf, MKK1/2 and ERK expression of THP-1 cells. In conclusion, ATRA suppressed Th2- and Th1-related chemokines expression in THP-1 cells, at least in part via the c-Raf-MKK1/2-ERK/MAPK pathway.

Tumor-like cerebral perivasculitis in a pediatric patient with systemic lupus erythematosus.

Nervous system manifestations are present in up to 70% of patients with systemic lupus erythematosus (SLE). The spectrum of clinical symptoms varies widely, from severe, life-threatening symptoms at presentation, such as transverse myelitis, to symptoms of more subtle and subclinical abnormalities of neurocognitive function. We report the case of a 14-year-old patient with SLE and lupus nephritis under regular steroid therapy, who had a sudden onset of consciousness change. Brain magnetic resonance imaging showed a huge mass lesion. After surgical decompression and corticosteroid pulse therapy, the patient's neurologic symptoms improved dramatically. Brain biopsy revealed perivasculitis of the brain with marked perivascular infiltration of eosinophils, macrophages, and neutrophils. Microhemorrhage was also evident. The patient recovered without obvious neurologic sequelae.

Changes in serum eotaxin and eosinophil cationic protein levels, and eosinophil count during treatment of childhood asthma.

BACKGROUND AND PURPOSE: Increased serum levels of eotaxin are related to the severity of asthma in adults. There are limited data on the effects of oral corticosteroids and inhaled corticosteroid therapy on serum levels of eotaxin and eosinophil cationic protein (ECP) and peripheral blood eosinophil counts (ECs) in pediatric asthma patients. We investigated prospectively the changes in eotaxin and ECP serum levels and peripheral blood ECs after administering oral corticosteroids and then inhaled corticosteroids plus long-acting beta2 agonist treatment in pediatric patients. METHODS: Serum samples of 20 pediatric patients with mild-to-moderate asthma were collected before treatment, after 5-7 days of oral prednisolone treatment, and after 1-2 months of inhaled fluticasone plus salmeterol treatment. Peak expiratory flow was used as the outcome index. RESULTS: Serum eotaxin levels remained the same after oral prednisolone treatment, but decreased after subsequent inhalation treatment compared with the end of oral steroid treatment (64.7 +/- 22.6 vs 85.7 +/- 36.8 pg/mL, p<0.001). The EC and serum ECP levels declined soon after oral steroid treatment, rebounding to initial levels during inhalation treatment. The decrease in ECP level was positively correlated with the decrease in ECs with oral steroid treatment (r(2) = 0.28, p=0.016). There was no correlation between changes in eotaxin levels and peak expiratory flow. CONCLUSIONS: Our data suggest that the serum eotaxin level, not peripheral blood EC or serum ECP level, declines during inhaled fluticasone plus salmeterol treatment and might serve as a surrogate marker of T helper 2 residual activity in pediatric asthma.

Painless massive ascites and hypoalbuminemia as the major manifestations of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is frequently associated with ascites, but rarely without proteinuria. We report a 10-year-old girl with distended, non-tender abdomen with shifting dullness and no pitting edema in the lower legs before admission. Facial rash had appeared 1-2 weeks before admission and became more prominent 3 days prior to admission. Hypoalbuminemia with hypertriglycemia (but no proteinuria or diarrhea) was noticed. The antinuclear antibody titer was 1:2560 (speckle type) and the anti-double-stranded DNA was 1:160. Abdominal echo revealed no cirrhosis change or venous obstruction. Chest X-ray and electrocardiogram revealed no cardiomegaly or pericardial effusion. The serum prealbumin was low on admission day 5, but the liver function tests were within normal range. We deduced that the hypoalbuminemia in SLE without nephritis may be secondary to mesenteric vascular leakage. SLE may present with initial manifestation of painless massive ascites. Careful utilization of history taking, chest X-ray, electrocardiogram, cardiac and abdominal echo, urinary analysis and serum prealbumin is helpful in decision-making while assessing such patients.

Neuronal intestinal dysplasia type B with massive small intestinal hemorrhage: report of one case.

Neuronal intestinal dysplasia type B is characterized by poor intestinal motility that usually results in constipation. Massive gastrointestinal hemorrhage is very unusual as the initial presentation in this disease entity. We report on a 3-year-and-7-month-old boy who had experienced two episodes of life-threatening lower gastrointestinal hemorrhage and high fever. Technetium-99m labeled red blood cell scan and the Meckel's diverticulum scan failed to demonstrate the bleeding point. The results of panendoscopy and colonoscopy were negative. Laparotomy revealed a 70 cm-long thick-walled intestine (from 100 cm to 170 cm below the Treitz ligament) with cord like material formed by mucosa debris, blood clot and mucus. Pathology report revealed hyperplastic nerve bundles in submucosal plexus with giant ganglion formation, consistent with neuronal intestinal dysplasia type B.

Long-acting beta 2 agonists suppress IP-10 expression in human bronchial epithelial cells.

BACKGROUND: Interferon-γ-inducible protein (IP)-10 (CXCL10) is an important chemokine secreted by the airway epithelium that functions as a biomarker for virus-induced asthma. Long-acting beta 2 (ß2) agonists (LABAs) are frequently used as inhaled medication for asthma and chronic obstructive pulmonary disease. However, previous research failed to investigate the effects of LABAs on IP-10 in bronchial epithelial cells. OBJECTIVE: To study the effects and signaling pathways of formoterol and salmeterol on polyriboinosinic polyribocytidylic acid (poly I:C)-induced IP-10 expression in BEAS-2B cells. METHODS: BEAS-2B cells were pretreated with formoterol and salmeterol for 2 hours before poly I:C stimulation. ICI 118551 (ß2 adrenoreceptor antagonist) or mitogen-activated protein kinase (MAPK) inhibitors were added 30 minutes before LABAs were added. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction were used to measure IP-10 protein and messenger RNA levels. Mitogen-activated protein kinase inhibitors and Western blotting were used to identify MAPK pathways, whereas bioassay revealed the MAPK functions. RESULTS: Long-acting ß2 agonists significantly down-regulated the poly I:C-induced IP-10 protein and messenger RNA expression in BEAS-2B cells. ICI 118551 reversed this effect. Forskolin, a cyclic adenosine monophosphate activator, produced a similar inhibitory effect. Western blotting showed that formoterol suppressed poly I:C-induced IP-10 expression via the c-Jun N-terminal kinase-c-Jun pathway. CONCLUSION: Long-acting ß2 agonists down-regulate poly I:C-induced IP-10 expression in BEAS-2B cells via the ß2 adrenoreceptor-cyclic adenosine monophosphate and c-Jun N-terminal kinase/c-Jun pathways. Long-acting ß2 agonists also inhibit IP-10 production in bronchial epithelial cells and may prolong viral elimination.

Suppressive effects of procaterol on expression of IP-10/CXCL 10 and RANTES/CCL 5 by bronchial epithelial cells.

As indicated in the Global Initiative for Asthma guidelines, short-acting ß2-adrenoreceptor agonists (SABAs) are important relievers in asthma exacerbation. Interferon γ-inducible protein (IP)-10/CXCL 10 is a T-helper type 1 (Th1) cell-related chemokine which is important in the recruitment of Th1 cells involved in host immune defense against intracellular pathogens such as viral infection. Regulated on activation, normal T expressed and secreted (RANTES)/CCL 5 is a chemokine which plays a role in attractant of eosinophils, mast cells, and basophils toward the site of allergic inflammation. Bronchial epithelial cells are first-line barriers against pathogen invasion. However, whether SABAs have regulatory effects on the expression of IP-10 and RANTES in bronchial epithelial cells is unknown. BEAS-2B cells, the human bronchial epithelial cell lines, were pretreated with procaterol (one of the SABAs) or dibutyryl-cAMP (a cyclic AMP analog) at different doses for 1 h and then stimulated with poly I:C (10 µg/mL). Supernatants were collected 12 and 24 h after poly I:C stimulation to determine the concentrations of IP-10 and RANTES by ELISA. In some cases, the cells were pretreated with selective ß2-adrenoreceptor antagonist, ICI-118551, 30 min before procaterol treatment. To investigate the intracellular signaling, the cells were pretreated with mitogen-activated protein kinase (MAPK) inhibitors and a NF-κB inhibitor 30 min before procaterol treatment. Western blot was also used to explore the intracellular signaling. Procaterol significantly suppressed poly I:C-induced IP-10 and RANTES in BEAS-2B cells in a dose-dependent manner. ICI-118551, a selective ß2-adrenoreceptor antagonist, could significantly reverse the suppressive effects. Dibutyryl-cAMP could confer the similar effects of procaterol on poly I:C-induced IP-10 and RANTES expression. Data of Western blot revealed that poly I:C-induced p-ERK, p-JNK, and pp38 expression, but not pp65, were suppressed by procaterol. SABAs could suppress poly I:C-induced IP-10 and RANTES expression in bronchial epithelial cells, at least in part, via ß2-adrenoreceptor-cAMP and MAPK-ERK, JNK, and p38 pathways.

Effects of PGI2 analogues on Th1- and Th2-related chemokines in monocytes via epigenetic regulation.

Chemokines play important roles in asthma. Prostaglandin I(2) (PGI(2)) analogue is recently suggested as a candidate for treating asthma. However, the effects of PGI(2) analogues on the expression of Th1- and Th2-related chemokines are unknown. To this end, we investigated the in vitro effects of PGI(2) analogues on the expression of Th1-related chemokine interferon-γ-inducible protein-10 (IP-10/CXCL10) and Th2-related chemokine macrophage-derived chemokine (MDC/CCL22) in human monocytes. The human monocytes were pretreated with iloprost and treprostinil before lipopolysaccharide (LPS) stimulation. IP-10 and MDC were measured by ELISA. Intracellular signaling was investigated by cyclic adenosine monophosphate (cAMP) assay, western blot and chromatin immunoprecipitation. PGI(2) analogues enhanced MDC, but suppressed IP-10 expression in LPS-stimulated monocytes. These effects were reversed by the I prostanoid (IP) receptor antagonist (CAY10449), peroxisomal proliferators-activated receptor (PPAR)-α antagonist (GW6741) and PPAR-γ antagonist (GW9662). PGI(2) analogues increased intracellular cAMP levels. Forskolin, an adenyl cyclase activator, conferred similar effects. PGI(2) analogue-enhanced MDC expression was reduced by nuclear factor (NF) κB inhibitor (BAY 117085) and mitogen-activated protein kinase (MAPK)-p38 inhibitor (SB203580). PGI(2) analogues up-regulated phospho-p65 and phospho-p38 but down-regulated phospho-ERK expression. Iloprost enhanced H3 acetylation in MDC promoter area and suppressed H3 acetylation, H3K4, and H3K36 trimethylation in IP-10 promoter area. PGI(2) analogues enhanced MDC expression via the I prostanoid-receptor-cAMP, PPAR-α and PPAR-γ, NFκB-p65, MAPK-p38-ATF2 pathways and increasing histone acetylation, and suppressed IP-10 expression via the IP-receptor-cAMP, PPAR-γ, MAPK-ERK-ELK1 pathways and inhibiting histone acetylation and trimethylation in LPS-stimulated monocytes. PGI(2) analogues may therefore increase Th2 recruitment and inflammation.

Effects of budesonide and fluticasone propionate in pediatric asthma patients.

BACKGROUND: Cytokines and chemokines play important roles in asthma. However, little information exists on the effects of inhaled corticosteroids on cytokine and chemokine plasma levels in childhood asthma. We compared the pharmaceutical effects of two inhaled corticosteroids used in pediatric patients with mild-to-moderate asthma, budesonide and fluticasone propionate. METHODS: Pediatric patients aged 5-18 years old were enrolled in this randomized, open-label, observer-blinded study and received 3 months of treatment with either inhaled budesonide (200 microg/puff) or fluticasone propionate (250 microg/puff), at two puffs per day. Peak expiratory flow (PEF), exhaled nitric oxide, Asthma Control Test (ACT), plasma Levels of tumor necrosis factor-alpha, thymus and activation-regulated chemokine, and interferon-inducible protein 10 were measured before treatment and monthly for 3 months after treatment. RESULTS: There were six patients in the budesonide group, and eight in the fluticasone group. After 3 months, both groups showed improved PEF. In the first month, PEF improved more in the budesonide group than in the fluticasone group, though the difference was not significant. After treatment, ACT scores in both groups were well controlled, except for one patient in the fluticasone group. The fluticasone group had a more significant reduction in exhaled nitric oxide than the budesonide group in the first month. CONCLUSION: Improvements in lung function were more rapid in the budesonide group than the fluticasone group. However, patients in the fluticasone group had better anti-inflammatory responses than those in the budesonide group. We conclude that each inhaled corticosteroids have its own clinical and laboratory effects.

Natural flavone kaempferol suppresses chemokines expression in human monocyte THP-1 cells through MAPK pathways.

There is increasing evidence that daily intake of flavonoids reduced severity and prevalence of allergic diseases. However, the mechanism of its antiinflammatory effects in allergic diseases remains uncertain. Kaempferol, which belongs to the flavone group, is a strong antioxidant among natural flavonoids and is the essential component of many beverages and vegetables. Because chemokine is one of the key mediators in allergic inflammatory process, we investigated the effect of kaempferol on chemokines expression in monocytes. Our data demonstrated that kaempferol significantly inhibited the lipopolysaccharide (LPS)-induced production of monocyte-derived chemokine (MDC), interferon gamma-induced protein 10 (IP-10), and interleukin-8 (IL-8) in THP-1 cells. Growth-related oncogene-α (GRO-α) was also suppressed at a higher concentration. We also found that kaempferol was able to suppress LPS-induced mitogen-activated protein kinase (MAPK) pathways, as well as the phosphorylation of upstream c-raf and MEK1/2. In brief, kaempferol suppressed LPS-induced T helper 1 (Th1), T helper 2 (Th2), and neutrophil-related chemokines production in monocytes might be via the MAPK pathways.

Effects of vitamin D3 on expression of tumor necrosis factor-alpha and chemokines by monocytes.

The association between vitamin D deficiency and asthma epidemic has been recognized. Tumor necrosis factor (TNF)-alpha and chemokines play important roles in pathogenesis of asthma. However, whether vitamin D has immunoregulatory function on TNF-alpha and chemokines expression in human monocytes is still unknown. The human monocytic cell line, THP-1 cells and human primary monocytes were pretreated with various concentration of 1alpha,25-(OH)(2)D(3) for 2 h before stimulation with lipopolysaccharide (LPS). Supernatants were collected 24 or 48 h after LPS stimulation. The levels of TNF-alpha, interferon-inducible protein 10 (IP-10)/CXCL10 (the Th1-related chemokine), macrophage-derived chemokine (MDC)/ CCL22 (the Th2-related chemokine), and interleukin 8 (IL-8)/CXCL8 (the neutrophil chemoattractant) were measured by ELISA. 1alpha,25-(OH)(2)D(3) could significantly suppress TNF-alpha and IP-10 expression in LPS-stimulated THP-1 and human primary monocytes. However, 1alpha,25-(OH)(2)D(3), especially in higher concentration, could significantly enhance MDC expression. 1alpha,25-(OH)(2)D(3) had no significant effects on IL-8 expression. We found 1alpha,25-(OH)(2)D(3) could significantly suppress TNF-alpha and Th1-related chemokine IP-10, which both play important roles in pathogenesis of severe refractory asthma and autoimmune diseases. However, 1alpha,25-(OH)(2)D(3) enhanced Th2-related chemokine MDC, which may result in Th2 inflammatory cell recruitment and thus adversely affect asthmatic patients. Although vitamin D has potential utility in the treatment of asthma and autoimmune diseases, excessive use of vitamin D may not be suitable in patients with Th2 allergic diseases.

Modulation of cytokine expression in human myeloid dendritic cells by environmental endocrine-disrupting chemicals involves epigenetic regulation.

BACKGROUND: Exposure to environmental endocrine-disrupting chemicals (EDCs) is often associated with dysregulated immune homeostasis, but the mechanisms of action remain unclear. OBJECTIVES: The aim of this study was to test a hypothesis that EDCs regulate the functions of human dendritic cells, a front-line, immunoregulatory cell type in contact with the environment. METHODS: We investigated circulating myeloid dendritic cells (mDCs) from five subjects and measured their responses, with or without coculture with autologous T cells, to two common EDCs, nonylphenol (NP) and 4-octylphenol (4-OP). EDC-associated cytokine responses, signaling events, and histone modifications were examined using ELISA, Western blotting, and chromatin immunoprecipitation (ChIP) assays, respectively. RESULTS: In all cases, mDCs treated with NP or 4-OP demonstrated increased expression of tumor necrosis factor-alpha (TNF-alpha) but decreased baseline and lipopolysaccharide (LPS)-induced (interleukin) (IL)-10 production; the increase in TNF-alpha was partially reversible by an estrogen receptor (ER) antagonist. Activation of the MKK3/6-p38 signaling pathway marked the effect of NP on TNF-alpha expression, concomitant with enhanced levels of methyltranferase complex [mixed-lineage leukemia (MLL) and tryptophan-aspartic acid repeat domain 5 (WDR5)] in the nucleus and of trimethylated H3K4, acetylated H3, and H4 at the TNFA gene locus. Further, up-regulated TNF-alpha expression was significantly suppressed in NP-treated mDCs by a histone acetyltransferase inhibitor. In the presence of NP-treated mDCs, T cells showed increased levels of IL-13 but decreased expression of interferon-gamma. CONCLUSIONS: These results suggest that NP and 4-OP may have functional effects on the response of mDCs via, in part, the ER, MKK3/6-p38 MAPK signaling pathway, and histone modifications, with subsequent influence on the T-cell cytokine responses.

Effect of procaterol on Th2-related chemokines production in human monocyte and bronchial epithelial cells.

Procaterol is a ß2-adrenoceptor agonist used as a bronchodilator for the treatment of asthma; it also possesses an anti-inflammatory property. As chemokines play a pivotal role in inflammation and the pathogenesis of asthma, we investigated the effects of procaterol on type 2 helper T cell (Th2)-related [macrophage-derived chemokine (MDC) and I-309] and type 1 helper T cell (Th1)-related chemokines [monokine-induced by IFN-gamma (Mig) and interferon-inducible protein 10 (IP-10)] production of THP-1 cells and human primary monocytes. The effect on thymus- and activation-regulated chemokine (TARC) production in BEAS-2B cells was also evaluated. Nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) inhibitors were used to ascertain the intracellular signal pathways involved, and etazolate, a phosphodiesterase 4 inhibitor, was used to assess the correlation between the ß2-adrenoceptor-cAMP pathway and the effect on chemokines. In addition, chromatin immunoprecipitation assays (ChIPs) were performed to detect histone modification in the TARC promoter region. MDC and I-309 production of both THP-1 cells and primary human monocytes, as well as TARC expression of BEAS-2B cells, were significantly inhibited by procaterol (10(-10)-10(-7) M); however, procaterol did not suppress Mig and IP-10 expression by THP-1 cells. MDC secreted by monocytes is associated with the NF-κB and MAPK signaling pathways, in particular p38- and c-Jun N-terminal kinase (JNK) MAPKs. Etazolate blocked the expression of MDC by THP-1 cells and TARC by BEAS-2B cells. ChIP assay revealed decreased trimethylation of lysine 4 in histone 3 (H3K4) in the TARC promoter region of BEAS-2B cells. In conclusion, procaterol could inhibit Th2-related chemokines production in human monocytes and bronchial epithelial cells, an effect that may be mediated through not only the NF-κB, p38, and JNK-MAPK pathways, but also the ß2-adrenoceptor-cAMP pathway. Most importantly, the suppressive effect of Th2-related chemokines production by procaterol might be regulated via post-transcriptional modification by decreasing H3K4 trimethylation.