Rabbit Anti-Mouse CLEC5A (a.a. 101-190) Polyclonal antibody

Background Previously, using microarrays and mRNA-Sequencing (mRNA-Seq) we found that occupational exposure to a range of benzene levels perturbed gene expression in peripheral blood mononuclear cells. Objectives In the current study, we sought to identify gene expression biomarkers predictive of benzene exposure below 1 part per million (ppm), the occupational standard in the U.S. Methods First, we used the nCounter platform to validate altered expression of 30 genes in 33 unexposed controls and 57 subjects exposed to benzene (<1 to >= 5 ppm). Second, we used SuperLearner (SL) to identify a minimal number of genes for which altered expression could predict <1 ppm benzene exposure, in 44 subjects with a mean air benzene level of 0.55 +/- 0.248 ppm (minimum 0.203ppm). Results nCounter and microarray expression levels were highly correlated (coefficients >0.7, p<0.05) for 26 microarray-selected genes. nCounter and mRNA-Seq levels were poorly correlated for 4 mRNA-Seq-selected genes. Using negative binomial regression with adjustment for covariates and multiple testing, we confirmed differential expression of 23 microarray-selected genes in the entire benzene-exposed group, and 27 genes in the <1 ppm-exposed subgroup, compared with the control group. Using SL, we identified 3 pairs of genes that could predict <1 ppm benzene exposure with cross-validated AUC estimates >0.9 (p<0.0001) and were not predictive of other exposures (nickel, arsenic, smoking, stress). The predictive gene pairs are PRG2/CLEC5A, NFKBI/CLEC5A, and ACSL1/CLEC5A. They play roles in innate immunity and inflammatory responses. Conclusions Using nCounter and SL, we validated the altered expression of multiple mRNAs by benzene and identified gene pairs predictive of exposure to benzene at levels below the US occupational standard of 1ppm.

Dengue virus (DENV) infection causes several diseases ranging from dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome characterized by endothelial dysfunction, vascular leakage, and shock. Here, we identify a potential mechanism by which DENV induces tissue injury and vascular leakage by promoting the activation of interleukin (IL)-1 beta. DENV facilitates IL-1 beta secretion in infected patients, mice, human peripheral blood mononuclear cells (PBMCs), mouse bone marrow-derived macrophages (BMDMs), and monocyte-differentiated macrophages (THP-1) via activating the NLRP3 inflammasome. The accumulated data suggest that IL-1 beta probably induces vascular leakage and tissue injury in interferon-alpha/beta receptor 1 deficient C57BL/6 mice (IFNAR(-/-) C57BL/6), whereas IL-1 receptor antagonist (IL-1RA) alleviates these effects of IL-1 beta. Finally, administration of recombinant IL-1 beta protein results in vascular leakage and tissue injury in C57BL/6 mice. Together, the accumulated results demonstrate that IL-1 beta contributes to DENV-associated pathology and suggest that IL-1RA acts as a potential agent for the treatment of DENV-associated diseases.