Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children

Background Vitamin D is known to have a number of immunological effects and it may play a role in preventing allergic diseases.
Objectives To study the effect of maternal intake of vitamin D during pregnancy on the emergence of asthma, allergic rhinitis (AR), and atopic eczema by the age of 5 years in children with HLA-DQB1-conferred susceptibility for type 1 diabetes.
Methods Children (1669) participating in the population-based birth cohort study were followed for asthma, AR, and atopic eczema assessed by validated questionnaire at 5 years. Maternal diet was assessed by a food-frequency questionnaire.
Results The mean maternal intake of vitamin D was 5.1 (SD 2.6) μg from food and 1.4 (2.6) μg from supplements. Only 32% of the women were taking vitamin D supplements. When adjusted for potential confounders, maternal intake of vitamin D from food was negatively related to risk of asthma [hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.64–0.99] and AR [HR 0.85; 95% CI 0.75–0.97]. Vitamin D supplements alone were not associated with any outcome. Adjustment for maternal intake of other dietary factors did not change the results.
Conclusion Maternal vitamin D intake from foods during pregnancy may be negatively associated with risk of asthma and AR in childhood.     

Interactions between epithelial cells and dendritic cells in airway immune responses: lessons from allergic airway disease

Micro-organisms constantly invade the human body and may form a threat to our health. Traditionally, concepts of defence mechanisms have included a protective outer layer of epithelia and a vigilant immune system searching for areas where the integrity of the outer layer may be compromised. Instead of considering these elements as two independent mechanisms, we should be treating them as a single integrated system. This review will present and discuss the role of local immune-competent cells and local epithelia in the recognition of potential pathogens and how the interaction between the two components may affect the initiation of the airway immune response. A concept emerges where airway mucosal dendritic cells act as integrators of both immunostimulatory and immunosuppressive signals that act within actively-involved mucosal tissue.     

Dietary vitamin D intake and vitamin D related genetic polymorphisms are not associated with gastric cancer in a hospital-based case-control study in Korea

There have been few studies on the association between vitamin D levels and gastric cancer in Asian populations, but no studies have been performed on the interactions between vitamin D intake and polymorphisms in the vitamin D pathway. The effects of vitamin D intake, vitamin D related genetic polymorphisms, and their association with the incidence of gastric cancer were investigated in a hospital case-control study, including 715 pairs of newly diagnosed gastric cancer patients and controls matched for age and sex. Correlations between vitamin D intake and plasma vitamin D concentrations were also assessed in a subset of subjects. No statistically significant difference was observed in the dietary intake of vitamin D between the patients and controls, nor were there any evident associations between vitamin D intake and risk of gastric cancer in multivariate analyses. Vitamin D intake significantly correlated with the circulating 25-hydroxyvitamin D levels, but not with the active form of the vitamin, 1,25-dihydroxyvitamin D. There were no statistically significant interactions between vitamin D intake, and VDR or TXNIP polymorphisms. This study suggests that dietary vitamin D intake is not associated with gastric cancer risk, and the genetic polymorphisms of vitamin D-related genes do not modulate the effect of vitamin D with respect to gastric carcinogenesis.     

Effects of vitamin E on human platelet and mononuclear cell responses in vitro

Recent epidemiological studies have provided evidence supporting the potential benefits of antioxidants in coronary prevention. We have investigated the effects of vitamin E on platelets, monocytes and endothelial cells in vitro. Pre-incubation of platelets with vitamin E inhibited subsequent thrombin- (P < 0.05, n = 5), collagen- (P < 0. 0001, n = 5) and ADP-(P < 0.05, n = 4) induced platelet aggregation measured using a microtitre plate method, or conventional aggregometry. The adhesion of thrombin-activated platelets to collagen was also inhibited by vitamin E (P < 0.05, n = 8), but not by vitamin C (P > 0.05, n = 8); nor was the adhesion of unstimulated platelets significantly affected (P > 0.05, n = 8). Pre-incubation of monocytes with vitamin E inhibited their subsequent adhesion to plastic (P < 0.05, n = 9), and was also associated with an 18% reduction in adhesion to EA.hy 926 endothelial cells (n = 8), although this failed to reach statistical significance. Pre-incubation of the endothelial cells with vitamin E also significantly reduced subsequent mononuclear cell adhesion by 56% (P < 0.05, n = 3).     

Downregulated Rac1 promotes apoptosis and inhibits the clearance of apoptotic cells in airway epithelial cells,which may be associated with airway hyper‐responsiveness in asthma

The accumulation of airway apoptotic cells may be an important factor causing airway hyper‐responsiveness (AHR). Whether the apoptotic cells can be promptly removed is related to the occurrence and course of asthma. In recent years, studies have shown that Rac1 is involved in many cellular biological activities including the formation and elimination of apoptotic cells. In this study, based on the analysis of airway local cells and related factors in asthmatic mice, we evaluated the expression of Rac1 in airway epithelial cells or phagocytes and analysed its relationship with the incidence of apoptosis or scavenging of apoptotic cells. Our data showed that the expression level of Rac1 in asthmatic mice decreased significantly, while the expression of IL‐33 increased obviously. The airway epithelial cell line was stimulated by curcumin at 50 μmol/L for 24‐48 hours; more than 50% of the cells were apoptotic, and of which, about 20% were late apoptosis. Rac1 inhibitor (NSC23766) can enhance the apoptosis effect. In addition, the ability of phagocytosis and migration in the epithelial cells or macrophages was increased following the application of Rac1 inhibitors or specific siRNA in a dose‐dependent manner, and the expression level of IL‐33 was simultaneously increased after blocking Rac1. It is suggested that the down regulation of Rac1 in asthma may contribute to the apoptosis of airway epithelial cells and affect the clearance of apoptotic cells, which will lead to the aggregation of the apoptotic cells in the respiratory tract and participate in AHR.     

Vitamin E down-modulates mitogen-activated protein kinases, nuclear factor-kappaB and inflammatory responses in lung epithelial cells

The airway epithelium plays an active role in acute lung inflammation by producing chemotactic factors and by expressing cell adhesion molecules involved in the migration of leucocytes to extravascular spaces. We have reported previously that neutrophil migration to airways can be down-modulated by exogenously administered vitamin E (α-tocopherol). The mechanism for this effect is not well understood, however. The action of α-tocopherol was investigated in human alveolar type II and bronchial epithelial cells stimulated with tumour necrosis factor-α. Treatment of alveolar epithelial cells with α-tocopherol resulted in down-regulated cell surface expression of intercellular adhesion molecule-1 (ICAM-1). On bronchial epithelial cells, both ICAM-1 and vascular adhesion molecule-1 were decreased, leading to diminished adherence of leucocytes to the cells. The production of the neutrophil chemoattractant interleukin-8 was attenuated in both alveolar and bronchial cells. These effects were preceded by reduced activation of the mitogen-activated protein kinases (MAPK), extracellular signal-regulated kinase (ERK1/2) and p38, as well as down-regulation of nuclear factor-κB. Comparing the effects of α-tocopherol with that of specific inhibitors of MAPK and protein kinase C (PKC) revealed that effects appear to be partly independent of PKC inhibition. These results implicate the anti-inflammatory action of α-tocopherol in addition to its anti-oxidant properties.     

Cigarette smoke increases Toll-like receptor 4 and modifies lipopolysaccharide-mediated responses in airway epithelial cells

Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke. The main goal of this study was to explore the effects of cigarette smoke extracts (CSE) on Toll-like receptor (TLR) expression and activation in a human bronchial epithelial cell line (16-HBE). The CSE increased the expression of TLR4 and the lipopolysaccharide (LPS) binding, the nuclear factor-kappaB (NF-kappaB) activation, the release of interleukin-8 (IL-8) and the chemotactic activity toward neutrophils. It did not induce TLR2 expression or extracellular signal-regulated signal kinase 1/2 (ERK1/2) activation. The LPS increased the expression of TLR4 and induced both NF-kappaB and ERK1/2 activation. The combined exposure of 16-HBE to CSE and LPS was associated with ERK activation rather than NF-kappaB activation and with a further increase of IL-8 release and of chemotactic activity toward neutrophils. Furthermore, CSE decreased the constitutive interferon-inducible protein-10 (IP-10) release and counteracted the effect of LPS in inducing both the IP-10 release and the chemotactic activity toward lymphocytes. In conclusion, cigarette smoke, by altering the expression and the activation of TLR4 via the preferential release of IL-8, may contribute to the accumulation of neutrophils within the airways of smokers.     

Adenovirus replication and host innate response in primary human airway epithelial cells

Background

Adenovirus infections are very common in children and sometimes fatal. Immune responses and hypercytokinemia are related to disease severity in patients with adenovirus infection. Understanding of viral replication and immune responses could help elucidate the immunopathogenesis of severe adenovirus infections.

Maternal diet during pregnancy: an emerging risk factor for childhood asthma

Evaluation of: Willers SM, Wijga AH, Brunekreef B et al. Maternal food consumption during pregnancy and the longitudinal development of childhood asthma. Am. J. Respir. Crit. Care Med. 178, 124–131 (2008).

It has been hypothesized that the recent marked increase in the prevalence of asthma may, in part, be a consequence of changing diet. There is increasing interest in the possibility that childhood asthma may be influenced by maternal diet during pregnancy and an increasing number of studies have highlighted associations between childhood asthma and maternal intake of certain foods (e.g., fish, fruits and vegetables) and nutrients (e.g., vitamin E, vitamin D, zinc and polyunsaturated fatty acids) during pregnancy. Maternal diet during pregnancy has the potential to influence fetal immune and airway development during a critical period of life with long-term irreversible consequences, such as childhood asthma. Further research, particularly intervention studies, needs to be carried out to establish whether dietary intervention during pregnancy can be used as a healthy, low-cost, public-health measure to reduce the prevalence of childhood asthma.     

Circulating 25‐hydroxyvitamin D,nasopharyngeal airway metabolome,and bronchiolitis severity

Low circulating 25‐hydroxyvitamin D (25OHD) levels are a risk factor for acute respiratory infection (eg, bronchiolitis) in children. However, little is known about the relation of circulating 25OHD with the many downstream functional molecules in target organs—such as the airway—and with clinical outcomes. In this prospective multicenter study of infants (age <1 year) hospitalized with bronchiolitis, we measured serum 25OHD levels and profiled the metabolome of 144 nasopharyngeal airway samples. Among 254 metabolites identified, we defined a set of 20 metabolites that are related to lower serum 25OHD and higher vitamin D‐binding protein levels. Of these metabolites, 9 metabolites were associated with a significantly higher risk of positive pressure ventilation use. These metabolites were glycerophosphocholines esterified with proinflammatory fatty acids (palmitate, arachidonate, linoleate, and stearate), sphingomyelins, alpha‐hydroxyisovalerate, 2‐hydroxybutyrate, and 3‐(4‐hydroxyphenyl)lactate (all FDR<0.05). Based on the multicenter data, vitamin D‐related airway metabolites were associated with risks of bronchiolitis severity.