Miwako Nasui

Involvement of the Cannabinoid CB2 Receptor and Its Endogenous Ligand 2-Arachidonoylglycerol in Oxazolone-Induced Contact Dermatitis in Mice

The possible involvement of 2-arachidonoylglycerol (2-AG), an endogenous ligand for the cannabinoid receptors (CB1 and CB2), in contact dermatitis in mouse ear was investigated. We found that the level of 2-AG was markedly elevated in the ear following a challenge with oxazolone in sensitized mice. Of note, the swelling following the challenge was suppressed by either the administration of SR144528, a CB2 receptor antagonist, immediately after sensitization, or the administration of SR144528 upon the challenge. The effect of AM251, a CB1 receptor antagonist, was marginal in either case. It seems apparent, therefore, that the CB2 receptor and its endogenous ligand 2-AG are closely involved in both the sensitization phase and the elicitation phase of oxazolone-induced contact dermatitis. In line with this, we found that Langerhans cells (MHC class II+) contain a substantial amount of CB2 receptor mRNA, whereas keratinocytes (MHC class II−) do not. We also obtained evidence that the expression of mRNAs for proinflammatory cytokines following a challenge with oxazolone was markedly suppressed by treatment with SR144528. We next examined whether the CB2 receptor and 2-AG participate in chronic contact dermatitis accompanied by the infiltration of tissues by eosinophils. The amount of 2-AG in mouse ear dramatically increased following repeated challenge with oxazolone. Importantly, treatment with SR144528 attenuated both the recruitment of eosinophils and ear swelling in chronic contact dermatitis induced by repeated challenge with oxazolone. These results strongly suggest that the CB2 receptor and 2-AG play important stimulative roles in the sensitization, elicitation, and exacerbation of allergic inflammation.

Distribution of γ-tubulin in multipolar spindles and multinucleated cells induced by dimethylarsinic acid, a methylated derivative of inorganic arsenics, in Chinese hamster V79 cells

Localization of γ-tubulin, a well-characterized component of microtubule-organizing centers (MTOCs), was investigated because of interest in the mechanism of the induction of aberrant mitotic spindles in Chinese hamster V79 cells exposed to dimethylarsinic acid (DMAA). In control cultures, γ-tubulin in interphase cells was located as a perinuclear dot on which the microtubules were nucleated. In metaphase cells, the location of γ-tubulin coincided with that of the mitotic spindle poles. DMAA caused mitotic delay and aberrant spindles, such as tripolar- and quadripolar spindles, in the mitotic cells. γ-Tubulin was co-localized with the aberrant spindles induced by DMAA. The incidence of γ-tubulin in the mitotic cells coincided with that of the aberrant spindles and rose with an increasing concentration of DMAA. By contrast, DMAA did not influence the number and location of γ-tubulin signals in interphase cells. These results suggest that multiple microtubule nucleation sites were induced by DMAA during transition from interphase to mitotic phase. DMAA-induced multiple signals of γ-tubulin were integrated into one signal at the center of multinucleated cells, surrounded by multiple nuclei as the cell cycle progressed to the next interphase, suggesting the presence of a self-integration mechanism of centrosomal MTOCs during the cell cycle.

Dielectric anomaly involving magnetic phase transition in a hexagonal antiferromagnet RbCoBr3

Abstract The dielectric and magnetic phase transitions in a triangular lattice antiferromagnet RbCoBr3 were studied by means of some dielectric, magnetic and calorimetric measurements. In this compound, which is a typical Ising-like antiferromagnet with antiferromagnetic moment along the hexagonal c-axis, a ferroelectric phase transition involving magnetic ordering with weak ferromagnetic moments confined in the c-plane was found to occur at T N(=37.OK). Those results imply that the magnetic ordering of this system is assisted by a polar lattice distortion, which can release partially the spin frustration due to the antiferromagnetic spin arrangement on a triangular lattice. This co-ordering is certainly ascribed to a probable competition between lattice-system and spin-system. Experimental data on this interesting phenomenon are presented and a possible mechanism is proposed.

Phase transitions and dielectric properties of hexagonal KNiCl3-type antiferromagnets

Abstract It is found that KNiCl3, RbFeBr3, RbMnBr3, RbCoBr3 and TlFeCl3 belonging to a KNiCl3-type antiferromagnet undergo novel class of structural phase transitions which comprise magnetic phase transitions accompanied by spin-frustration in the c-plane and ferroelectric one. They have a prototype crystal structure of space group symmetry P63 Immc and change this symmetry to hexagonal P63 cm or trigonal P Cl. Simultaneously, the configuration of the three kinds of the linear chains of face-sharing NiCl6-octahedra (h-h-h-packing) is displaced along the c-axis at the structural phase transitions. These compounds exhibit characteristic variations of the dielectric constant ε c , lattice constant c and spontaneous polarization P s in the structural and magnetic transitions. The compounds mentioned above and RbVBr3 are classified into three groups with respect to their dielectric and magnetic properties associated with the transitions. It is in particular interesting that RbCoBr3 develops simultaneously the ferroelectric and antiferromagnetic phase transitions at 37.OK.

Neu1 sialidase interacts with perilipin 1 on lipid droplets and inhibits lipolysis in 3T3-L1 adipocytes

Fatty acids are stored within adipocytes in lipid droplets (LDs) as triacylglycerol (TG), which is converted to free fatty acid (FFA) and glycerol via lipolysis. Increased plasma FFA levels in obesity are associated with several clinical conditions. We previously found that Neu1 activity is aberrant in the epididymal fat and liver of obese and diabetic mice. Here, we examined involvement of Neu1 in lipolysis in 3T3‐L1 adipocytes. Small interfering RNA against Neu1 was introduced into adipocytes, and glycerol concentrations were measured in the culture medium. We then assessed the effects of Neu1 knockdown on lipolytic protein expression and phosphorylation, as well as interactions between perilipin 1 (Plin1) and hormone‐sensitive lipase (HSL) after isoproterenol (IS) stimulation. Interactions between Neu1 and Plin1 were analyzed by immunoprecipitation and immunofluorescent imaging using adipocytes transfected with pCMV6‐mNeu1‐myc‐DYKDDDDK (mNeu1DDK). Neu1 knockdown increased glycerol concentrations in culture media and Plin1 phosphorylation in whole lysates of IS‐stimulated cells. Neu1 knockdown increased interaction between Plin1 and HSL after IS stimulation whereas that between Neu1 and Plin1 on LD observed under basal conditions was lost. These results suggest that Neu1 inhibits lipolysis induced by β‐adrenergic stimulation in adipocytes via interactions with Plin1 on LD.

Magnetic and dielectric properties of KNiCl3-type triangular lattice antiferromagnets with lattice distortion

Abstract By measuring dielectric constant and linear thermal expansion magnetic phase transitions of KNiCl 3 -type antiferromagnets are studied from a view point of distortion of the triangular lattice in the basal c -plane which is induced by structural phase transitions.

NEU1 sialidase controls gene expression and secretion of IL-6 and MCP-1 through NF-κB pathway in 3T3-L1 adipocytes

A sialidase NEU1 that removes sialic acids from glycoconjugates has been implicated in diverse cellular functions. Aberrant NEU1 activity is associated with various pathologies including lysosomal storage disorder sialidosis, autoimmune diseases and the malignancy and metastasis of cancer cells. We recently reported that NEU1 activity increases during 3T3-L1 adipogenesis and that it is higher in the epididymal fat of obese and diabetic mice. However, the precise functions of NEU1 in adipocytes have not been elucidated. Knockdown of NEU1 using siRNA transfection in 3T3-L1 adipocytes significantly decreased the mRNA expression and protein secretion of IL-6 and MCP-1 induced by LPS. The promoter activities of both IL-6 and MCP-1 as well as nuclear factor-kappa B (NF-κB) nuclear translocation were reduced in adipocytes transfected with an siRNA sequence that targets NEU1(siNEU1). NEU1 suppression using siNEU1 affected TLR4 sialylation. These findings suggest that NEU1 is involved in the production of IL-6 and MCP-1 in adipocytes possibly through TLR4/NF-κB signalling.