Human Anti-Human OSMR beta monoclonal Antibody, clone SFB948 [APC]

The interleukin (IL)-6/gp130 family of cytokines (e.g., IL-6, IL-11, leukemia inhibitory factor (LIF) and oncostatin M (OSM)) play important roles in the central nervous system (CNS) during neuroinflammation and neurodevelopment. However, little is known regarding the responses by astroglia and microglia to this family of cytokines. Here the expression of the IL-6/gp130 cytokine receptors and subsequent signal pathway activation was examined in murine astrocytes and microglia in vitro. Astrocytes had high levels of OSMR mRNA while lower levels of IL-6R, LIFR and IL-11R mRNAs were also present. In comparison, in microglia there was no detectable OSMR mRNA, higher levels of IL-6R mRNA and lower levels of the LIFR and IL-11R mRNAs. The OSMR protein was present in astrocytes but was undetectable in microglia. Conversely, the IL-6R protein was present in microglia but not detectable in astrocytes. In astrocytes but not microglia, phosphorylation of STAT1 and STAT3 occurred in response to OSM, whereas both microglia and astrocytes responded to hyper-IL-6 (IL-6 linked to the soluble IL-6 receptor). Finally, in both microglia and astrocytes, OSM failed to activate NFB or induce iNOS and nitrite production. We conclude: (1) notable differences exist in the expression of receptors utilized by the IL-6/gp130 family of cytokines in astrocytes and microglia, and (2) the findings provide a molecular basis for the differential response to OSM by astrocytes versus microglia and demonstrate a fundamental means for achieving cellular specificity in the response of these glial cells to this cytokine. GLIA 2015;63:132-141

Recent genome-wide association studies have identified various genetic variants associated with hematological traits. Although it is possible that quantitative data of hematological traits are varied among the years examined, conventional genome-wide association studies have been conducted in a cross-sectional manner that measures traits at a single point in time. To address this issue, we have traced blood profiles in 4,884 Japanese individuals who underwent annual health check-ups for several years. In the present study, longitudinal exome-wide association studies were conducted to identify genetic variants related to 13 hematological phenotypes. The generalized estimating equation model showed that a total of 67 single nucleotide polymorphisms (SNPs) were significantly [ false discovery rate (FDR) of < 0.01] associated with hematological phenotypes. Of the 67 SNPs, nine SNPs were identified as novel hematological markers: rs4686683 of SENP2 for red blood cell count (FDR = 0.008, P = 5.5 x 10(-6)); rs3917688 of SELP for mean corpuscular volume (FDR = 0.005, P = 2.4 x 10(-6)); rs3133745 of C8orf37-AS1 for white blood cell count (FDR = 0.003, P = 1.3 x 10(-6)); rs13121954 at 4q31.2 for basophil count (FDR = 0.007, P = 3.1 x 10(-5)); rs7584099 at 2q22.3 (FDR = 2.6 x 10(-5), P = 8.8 x 10(-8)), rs1579219 of HCG17 (FDR = 0.003, P = 2.0 x 10(-5)), and rs10757049 of DENND4C (FDR = 0.008, P = 5.6 x 10(-5)) for eosinophil count; rs12338 of CTSB for neutrophil count (FDR = 0.007, P = 2.9 x 10(-5)); and rs395967 of OSMR-AS1 for monocyte count (FDR = 0.008, P = 3.2 x 10(-5)).