CD14 -550 C/T, which is related to the serum level of sCD14, is associated with the development of RSV bronchiolitis in the Japanese population. This study's results indicate that, in different ethnic groups, different genetic factors contribute to the development of RSV bronchiolitis.
PGD2 has long been implicated in allergic diseases. Recent cloning of a second PGD2 receptor, DP2 (also known as CRTh2), led to a greater understanding of the physiological and pathophysiological implications of PGD2. PGD2 signaling through DP1 and DP2 mediates different and often opposite effects in many cell types of the immune system. Although mast cells (MC) are the largest source of PGD2 in the body, there is little information about their potential expression of DP2 and its functional significance. In this study, we show that tissue MC in human nasal polyps express DP2 protein, and that human MC lines and primary cultured human MC express mRNA as well as protein of DP2. By immunohistochemistry, we detected that 34% of MC in human nasal polyps expressed DP2. In addition, flow cytometry showed that 87% of the LAD2 human MC line and 98% of primary cultured human MC contained intracellular DP2. However, we could not detect surface expression of DP2 on human MC by single cell analysis using imaging flow cytometry. Blocking of endogenous PGD2 production with aspirin did not induce surface expression of DP2 in human MC. Two DP2 selective agonists, DK-PGD2 and 15R-15-methyl PGD2 induced dose-dependent intracellular calcium mobilization that was abrogated by pertussis toxin, but not by three DP2 selective antagonists. MC mediator release including degranulation was not affected by DP2 selective agonists. Thus, human MC express DP2 intracellularly rather than on their surface, and the function of DP2 in human MC is different than in other immune cells such as Th2 cells, eosinophils and basophils where it is expressed on the cell surface and induces Th2 cytokine and/or granule associated mediator release. Further studies to elucidate the role of intracellular DP2 in human MC may expand our understanding of this molecule and provide novel therapeutic opportunities.
Background: Transforming growth factor (TGF)-β in breast milk is crucial for mucosal immune system in the neonatal period. We hypothesized that the level of exposure to TGF-β from breast milk in the first month of life is related to the development of eczema later in life. Thus, the present study investigated whether changes in TGF-β levels between colostrum and mature milk are associated with such occurrence in a birth cohort study.Methods: Colostrum and 1-month breast milk samples were collected from mothers who participated in our birth cohort study. TGF-β1 and TGF-β2 levels in breast milk were measured using a commercial ELISA kit. The development of eczema in the first 6 months after birth was assessed based on parent's response to a questionnaire. Levels of TGF-β1 and TGF-β2 were compared in breast milk from mothers of infants with and without eczema.Results: In children with eczema, TGF-β1 levels were higher in colostrum, but lower in 1-month milk. A lower TGF-β1 ratio (1-month milk/colostrum) was related to the development of eczema during the first 6 months of life. There was no difference in TGF-β2 ratio (1-month milk/colostrum) between eczema group and control group.Conclusions: Concentration of TGF-β1 but not TGF-β2 in breast milk during the first month after birth may be associated with eczema later in life. Factors that increase TGF-β1 levels in breast milk may play a role in preventing allergic disease.
The regulatory IL-10 and TGF-beta1 cytokine gene polymorphisms have been associated with allergic diseases in different populations, like Caucasian, Chinese and Indians. We investigated the association between the polymorphisms IL-10 A-1082G, C-819T, C-627A and TGF-beta1 T+869C, G+915C, C-509T and food allergy in Japanese children. One hundred and eleven children with food allergy and 115 atopic control children without food allergy were recruited. DNA samples from these subjects were genotyped by using PCR. The odds ratio of IL-10 -1082 AA genotype was 2.5 (95% CI, 1.0-6.4) for food allergy risk when compared with atopic control subjects (p = 0.03). There were no significative differences in the frequency of TGF-beta1 gene polymorphisms between both groups. Our results indicate that IL-10 A-1082G gene polymorphism is associated with food allergy susceptibility in atopic Japanese children.
These findings show an association between CRTh2 rs533116 and allergic asthma and suggest this may be mediated by elevated expression of CRTh2, leading to higher numbers of circulating eosinophils and Th2 cytokine production.
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