Actin beta was chosen as internal normalization gene

n examination of cytokine and chemokine RNA and protein levels suggests that multiple pathways underlie the FITC-induced inflammation and are regulated, in part, the CRTH2 activation. These reductions in cytokines and chemokines are consistent with the gross reduction in ear thickness observed, as well as the histology, which shows a rather limited inflammatory infiltrate upon treatment with the higher doses of Cmpd A. Taken together, these observations underscore the pivotal role of the CRTH2PGD2 interaction in regulating allergen-induced cutaneous inflammation. However, a complete reduction in pro-inflammatory mediators was not observed with Cmpd A administration. This may be due, in part, to other proinflammatory mediators released by activated mast cells or the pharmacokinetic/pharmacodynamic profile of Cmpd A in mice. Nonetheless, these observations suggest that an overall reduction, but not necessarily a complete abrogation, of pro-inflammatory cytokine and chemokine production may be sufficient to severely dampen the cutaneous inflammatory response and the ensuing tissue pathology. Further, these studies suggest that antagonism of CRTH2 may be a potentially useful strategy in the therapeutic intervention of allergic disease. Funding National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. Measures of prenatal adversity have been associated with adult disease,1 but identifying the causal factors has been challenging.2 Quasi-experimental studies using the setting of the of the Dutch Hunger Winter of 194445,3 a 6-month famine, show that exposure to famine during pregnancy may increase the risk of obesity, type 2 diabetes, dyslipidaemia and schizophrenia in the offspring, and have highlighted early gestation as a sensitive period.4 In animal experiments, perturbation of prenatal nutrition has been shown to alter epigenetic marks such as DNA methylation which control stable changes in gene expression potential5 and are associated with adult phenotype.6 Experiments perturbing early maternal nutrition have shown that blastocyst development and the period around implantation is a critical developmental PR 619 window during which DNA methylation differences may arise.7,8 This may be related to the dynamic nature of DNA methylation during this period, as the genome is demethylated after fertilization and remethylated in the period after implantation.9 Most animal studies, however, evaluate nutritional perturbations across gestation in relation to DNA methylation differences.10,11 In humans, we have shown that prenatal famine exposure is associated with persistent differences in DNA methylation in adulthood and that the relation can depend on of the gestational timing of the exposure.12,13 We previously only examined famine exposure during the first or last 10 weeks of gestation in a candidate gene approach12,13 and the first 10 weeks in a genome-scale study.14 Studies by us and others on prenatal famine,1215 seasonal food shortage16 and micro-nutrient supplementation17,18 have focused on early gestation as being one period that is critically sensitive in this respect. DNA methylation differences may also arise later in gestation, for example from smoking during pregnancy.19 It is unknown during which other specific periods of gestation the human methylome may be sensitive to PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19826115 prenatal perturbations in nutrition, as a systematic genomewide investigation is still missing. Here we report on an epigenome-wide a