Possible association between Interleukin-1beta gene and schizophrenia in a Japanese population

Background: Several lines of evidence have implicated the pro-inflammatory cytokine interleukin-1beta (IL-1 beta) in the etiology of schizophrenia. Although a number of genetic association studies have been reported, very few have systematically examined gene-wide tagging polymorphisms. Methods: A total of 533 patients with schizophrenia (302 males: mean age +/- standard deviation 43.4 +/- 13.0 years; 233 females; mean age 44.8 +/- 15.3 years) and 1136 healthy controls (388 males: mean age 44.6 +/- 17.3 years; 748 females; 46.3 +/- 15.6 years) were recruited for this study. All subjects were biologically unrelated Japanese individuals. Five tagging polymorphisms of IL-1 beta gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were examined for association with schizophrenia. Results: Significant difference in allele distribution was found between patients with schizophrenia and controls for rs1143633 (P = 0.0089). When the analysis was performed separately in each gender, significant difference between patients and controls in allele distribution of rs1143633 was observed in females (P = 0.0073). A trend towards association was also found between rs16944 and female patients with schizophrenia (P = 0.032). Conclusions: The present study shows the first evidence that the IL-1 beta gene polymorphism rs1143633 is associated with schizophrenia susceptibility in a Japanese population. The results suggest the possibility that the influence of IL-1 beta gene variations on susceptibility to schizophrenia may be greater in females than in males. Findings of the present study provide further support for the role of IL-1 beta in the etiology of schizophrenia

Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults

<p>Abstract</p> <p>Background</p> <p>Recently, hypothalamus-pituitary-adrenal (HPA) axis function assessed with the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test has been shown to be associated with response to antidepressant treatment. A polymorphism (rs16944) in the interleukin-1beta (<it>IL-1β</it>) gene has also been reported to be associated with the medication response in depression. These findings prompted us to examine the possible association between <it>IL-1β </it>gene polymorphisms and HPA axis function assessed with the DEX/CRH test.</p> <p>Methods</p> <p>DEX/CRH test was performed in 179 healthy volunteers (45 males: mean age 40.5 ± 15.8 years; 134 females: mean age 47.1 ± 13.2 years). Five tagging single nucleotide polymorphisms (SNPs) of <it>IL-1β </it>gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were selected at an r²threshold of 0.80 with a minor allele frequency > 0.1. Genotyping was performed by the TaqMan allelic discrimination assay. A two-way factorial analysis of variance (ANOVA) was performed with the DEX/CRH test results as the dependent variable and genotype and gender as independent variables. To account for multiple testing, <it>P </it>values < 0.01 were considered statistically significant for associations between the genotypes and the cortisol levels.</p> <p>Results</p> <p>The cortisol levels after DEX administration (DST-Cortisol) showed significant associations with the genotypes of rs16944 (<it>P </it>= 0.00049) and rs1143633 (<it>P </it>= 0.0060), with no significant gender effect or genotype × gender interaction. On the other hand, cortisol levels after CRH administration (DEX/CRH-Cortisol) were affected by gender but were not significantly influenced by the genotype of the examined SNPs, with no significant genotype × gender interaction.</p> <p>Conclusions</p> <p>Our results suggest that genetic variations in the <it>IL-1β </it>gene contribute to the HPA axis alteration assessed by DST-Cortisol in healthy subjects. On the other hand, no significant associations of the <it>IL-1β </it>gene polymorphisms with the DEX/CRH-Cortisol were observed. Confirmation of our findings in futures studies may add new insight into the communication between the immune system and the HPA axis.</p

Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells

In vertebrates, newly emerging transformed cells are often apically extruded from epithelial layers through cell competition with surrounding normal epithelial cells. However, the underlying molecular mechanism remains elusive. Here, using phospho-SILAC screening, we show that phosphorylation of AHNAK2 is elevated in normal cells neighboring RasV12 cells soon after the induction of RasV12 expression, which is mediated by calcium-dependent protein kinase C. In addition, transient upsurges of intracellular calcium, which we call calcium sparks, frequently occur in normal cells neighboring RasV12 cells, which are mediated by mechanosensitive calcium channel TRPC1 upon membrane stretching. Calcium sparks then enhance cell movements of both normal and RasV12 cells through phosphorylation of AHNAK2 and promote apical extrusion. Moreover, comparable calcium sparks positively regulate apical extrusion of RasV12-transformed cells in zebrafish larvae as well. Hence, calcium sparks play a crucial role in the elimination of transformed cells at the early phase of cell competition

Mitochondrial dynamics in neurodegeneration.

It has been only 15 years since studies began on the molecular mechanisms underlying mitochondrial fission and fusion using simple model organisms such as Drosophila, yeast, and Caenorhabditis elegans. Beyond the primary functions of mitochondrial fission and fusion in controlling organelle shape, size, and number, it became clear that these dynamic processes are also critical to regulating cell death, mitophagy, and organelle distribution. Now, studies suggest that prominent changes occur in mitochondrial dynamics in a broad array of neurodegenerative diseases, and there is substantial evidence suggesting a key role in disease pathogenesis because neurons are among the most energy-consuming cell types and have a highly developed cell shape. Here, we review the recent findings on mitochondrial dynamics in neurodegeneration

Mitochondrial dynamics in neurodegeneration.

It has been only 15 years since studies began on the molecular mechanisms underlying mitochondrial fission and fusion using simple model organisms such as Drosophila, yeast, and Caenorhabditis elegans. Beyond the primary functions of mitochondrial fission and fusion in controlling organelle shape, size, and number, it became clear that these dynamic processes are also critical to regulating cell death, mitophagy, and organelle distribution. Now, studies suggest that prominent changes occur in mitochondrial dynamics in a broad array of neurodegenerative diseases, and there is substantial evidence suggesting a key role in disease pathogenesis because neurons are among the most energy-consuming cell types and have a highly developed cell shape. Here, we review the recent findings on mitochondrial dynamics in neurodegeneration