Biomedical Research
Online ISSN : 1880-313X
Print ISSN : 0388-6107
ISSN-L : 0388-6107
38 巻 , 3 号
選択された号の論文の9件中1~9を表示しています
Full Papers
  • Fuminori KAWABATA, Yuko KAWABATA, Ruojun LIANG, Shotaro NISHIMURA, Sho ...
    2017 年 38 巻 3 号 p. 149-155
    発行日: 2017/06/01
    公開日: 2017/06/20
    ジャーナル フリー

    Postprandial hyperglycemia is a risk factor for cardiovascular diseases. It has been reported that intragastric administration of allyl isothiocyanate (AITC), which is one of the pungent ingredients of wasabi and horseradish but it is not included in hot chili pepper, increased carbohydrate oxidation and reduced postprandial increase of blood glucose via transient receptor potential vanilloid 1 (TRPV1)in mice. However, the action site of AITC on TRPV1 for increasing carbohydrate oxidation is unclear. Both mammalian and chicken TRPV1 (cTRPV1) are activated by heat and acid, but unlike its mammalian counterpart, cTRPV1 is only faintly activated by capsaicin. This difference is due to the 8 chicken-specific amino acid residues around transmembrane 3, which is the main site of capsaicin-binding in rat TRPV1. Moreover, AITC-induced activation of mouse TRPV1 (mTRPV1) is largely dependent on S513, a residue that is involved in capsaicin-binding. Thus, we hypothesized that the increase of carbohydrate oxidation by AITC in mammals is induced by the binding of AITC to the capsaicin-binding site of TRPV1. In this study, we performed a comparative study using chickens and mice, since chickens are thought to partly lack the capsaicin-binding site of TRPV1. We examined the effects of AITC on the respiratory quotient (RQ), the index of carbohydrate oxidation and fat oxidation, in chickens and mice. Respiratory gas analysis revealed that AITC does not increase the RQ in chickens, and Ca2+ imaging methods and a whole cell-patch clamp analysis showed that AITC does not activate cTRPV1. These results implied that the capsaicin-binding site is an important region for increasing carbohydrate oxidation by AITC administration in animals.

  • Aya HIRAYAMA, Shuji AWANO, Yuji SETA, Toshihiro ANSAI
    2017 年 38 巻 3 号 p. 157-165
    発行日: 2017/06/01
    公開日: 2017/06/20
    ジャーナル フリー

    A disintegrin and metalloprotease 17 (ADAM17) is a tumor necrosis factor (TNF)-converting enzyme and was first identified as the enzyme that cleaves the prodomain of TNF-α, a proinflammatory cytokine that plays a central role in immune regulation and a variety of inflammatory responses in destructive periodontal disease. The aim of the present study was to verify the presence of ADAM17 in the gingival epithelium and elucidate its involvement in the release of TNF-αin oral keratinocytes. Immunohistochemical analyses of ADAM17 were performed in gingival tissues obtained from patients and in human oral keratinocytes (HOKs). Additionally, levels of TNF-α and ADAM17 in HOKs exposed to lipopolysaccharide (LPS) were assessed using enzyme-linked immunosorbent assays. Moreover, the effects of ADAM17 inhibitor, matrix metalloproteinase (MMP) inhibitor, and ADAM17 siRNA on TNF-α concentration were assessed. Strong immunoreactivity for ADAM17 was observed in the epithelium of the inflamed gingival tissues and in HOKs. Furthermore, treatment with either ADAM17 inhibitor or ADAM17 siRNA inhibited the generation of TNF-α induced by LPS in HOKs. The present study demonstrates that ADAM17 is strongly expressed in the epithelium of gingival tissues and suggests that ADAM17 may be a key enzyme that regulates the generation of TNF-α in oral keratinocytes.

  • Hiroyuki TADA, Takamitsu SHIMIZU, Kenji MATSUSHITA, Haruhiko TAKADA
    2017 年 38 巻 3 号 p. 167-173
    発行日: 2017/06/01
    公開日: 2017/06/20
    ジャーナル フリー

    hCAP-18/LL-37 is an antimicrobial peptide that is mainly expressed in epithelial cells. Gingival epithelial cells play pivotal roles in antimicrobial defense by expressing hCAP-18/LL-37. Porphyromonas gingivalis is a primary pathogen for chronic periodontitis and produces cysteine proteinase gingipains, which induce proinflammatory cytokines production, leading to enhance inflammatory responses. In contrast, gingipains attenuate immune responses, leading to induce anti-inflammatory responses. In this study, we investigated the ability of gingipains to attenuate P. gingivalis-induced hCAP-18/LL-37 production by human gingival epithelial Ca9-22 cells. The expression of LL-37 mRNA was increased by the infection of Ca9-22 cells with a P. gingivalis gingipains-null mutant KDP136 compared with P. gingivalis wild-type strain ATCC 33277. Interleukin (IL)-33 is involved in the development of chronic inflammatory diseases, and P. gingivalis infection increases IL-33 production by human gingival epithelial cells. P. gingivalis-induced LL-37 mRNA expression was augmented in IL-33 small interfering RNA-transfected Ca9-22 cells. Maxacalcitol (22-oxacalcitriol: OCT) is a biologically active metabolite of vitamin D3 analog, and OCT increases hCAP-18/LL-37 production by human gingival epithelial cells. The increasing expression of LL-37 mRNA by OCT was down-regulated by infection of the cells with P. gingivalis ATCC 33277 in Ca9-22 cells. Furthermore, P. gingivalis infection induced IL-33 mRNA expression in Ca9-22 cells; therefore, P. gingivalis-induced endogenous IL-33 down-regulated hCAP-18/LL-37 production by the bacterium. These findings suggested that endogenous IL-33 down-regulates the induction of hCAP-18/LL-37 production in human gingival epithelial cells.

  • Hideaki SUZUKI, Yuuko KOSUGE, Koji KOBAYASHI, Yoshifumi KUROSAKI, Naoh ...
    2017 年 38 巻 3 号 p. 175-182
    発行日: 2017/06/01
    公開日: 2017/06/20
    ジャーナル フリー

    Increase of thrombus in the coronary arteries is positively correlated with the level of heat-shock protein 72 (HSP72) in the blood of patients with acute myocardial infarction (AMI). Platelet aggregation participates in thrombus formation on ruptured plaque in AMI. In this study, we aimed to clarify the role of HSP72 in thrombus formation by evaluating the effects of HSP72 on platelet aggregation. Platelet aggregation activities were measured in platelet-rich plasma obtained from male Sprague-Dawley rats with or without the platelet activators, such as adenosine diphosphate (ADP), collagen, thrombin receptor-activating peptide-6 (TRAP-6), ristocetin, and arachidonic acid. Changes in aggregation were estimated by the co-addition of recombinant HSP72 and anti-HSP72 antibodies. Our results showed that addition of HSP72 increased platelet aggregation in the presence of low concentrations of ADP, collagen, TRAP-6, ristocetin, and arachidonic acid. Increased platelet aggregation stimulated by ADP and HSP72 was reduced by the co-addition of anti-HSP72 antibodies. Thus, these findings suggested that HSP72 was released extracellularly in response to stress, promoting thrombus formation and AMI. Additionally, treatment with anti-HSP72 antibodies may control platelet aggregation induced by extracellular HSP72.

  • Koji HOSHINO, Kan HASEGAWA, Haruyuki KAMIYA, Yuji MORIMOTO
    2017 年 38 巻 3 号 p. 183-188
    発行日: 2017/06/01
    公開日: 2017/06/20
    ジャーナル フリー

    Interleukin-1β (IL-1β) is a key molecule in the inflammatory responses elicited during infection and injury. It exerts local effects on synaptic plasticity by binding to IL-1 receptors that are expressed at high levels in the hippocampus. We examined the effects of IL-1β on synaptic plasticity in different hippocampal regions in acute mouse brain slices by measuring long-term potentiation (LTP). IL-1β (1 ng/mL) was applied for 30 min before LTP was induced with high-frequency stimulation (HFS). LTP was significantly impaired by either IL-1β application to the Schaffer collateral-CA1 synapses or the associational/commissural (A/C) fiber-CA3 synapses, which are both dependent on N-methyl-D-aspartate (NMDA) receptor activation. However, mossy fiber-CA3 LTP, which is expressed presynaptically in an NMDA-independent manner, was not impaired by IL-1β. Our results demonstrate that IL-1β exerts variable effects on LTP at different kinds of synapses, indicating that IL-1β has synapse-specific effects on hippocampal synaptic plasticity.

  • Hiroyuki TADA, Risako SUZUKI, Eiji NEMOTO, Hidetoshi SHIMAUCHI, Kenji ...
    2017 年 38 巻 3 号 p. 189-195
    発行日: 2017/06/01
    公開日: 2017/06/20
    ジャーナル フリー

    Interleukin-33 (IL-33) is an IL-1 cytokine family member that is involved in the development of chronic inflammatory diseases and the initiation of allergic inflammation in response to pathogens. Porphyromonas gingivalis is a primary pathogen that is involved in chronic periodontitis and its bacterial components induce inflammatory responses. Dendritic cells (DCs) recognize pathogen- associated molecular patterns by expression of pattern-recognition receptors, such as Toll-like receptors (TLRs). DCs play an essential role in resistance to infection and maintenance of mucosal immune system. In this study, we investigated whether P. gingivalis increases the expression of IL-33 in mouse bone marrow-derived DCs (BMDCs). BMDCs exhibited an increased expression of IL-33 mRNA upon stimulation with P. gingivalis whole cells. Furthermore, fimbriae and lipopeptide derived from P. gingivalis exhibited higher IL-33 mRNA expression than P. gingivalis whole cells. In contrast, lipopolysaccharide derived from P. gingivalis did not induce IL-33 mRNA expression in BMDCs. The IL-33 mRNA expression after stimulation with fimbriae or lipopeptide was up-regulated in BMDCs from wild-type mice but not from TLR2-deficient (TLR2−/−) mice. IL-33 production induced by fimbriae and lipopeptide accumulated in the cytoplasm of BMDCs from wild-type mice, but not from TLR2−/− mice. These findings suggested that IL-33 production induced by P. gingivalis fimbriae and lipopeptide is recognized by TLR2 and may modulate DC function in periodontal diseases.

  • Tomohiro CHIBA, Hirokazu NARITA, Hiroshi SHIMODA
    2017 年 38 巻 3 号 p. 197-205
    発行日: 2017/06/01
    公開日: 2017/06/20
    ジャーナル フリー

    Little information has been available regarding microanatomy of human thoracic duct in spite of the importance for an understanding of pathophysiology in clinical medicine. The present study demonstrated a fine structure of human thoracic duct system by light and scanning electron microscopy. A number of longitudinal or spiral ridges and grooves were formed on luminal surfaces of the lymphangia and lymph sac, it likely facilitating fluent lymph flow. The endothelial cells displayed various cell shapes in compliance with their distributed regions. The lymph sac joining large vein composed a peculiar multiple valve structure presumably ensuring lymph storage and prevention of lymph backflow. The longitudinal muscle sheet in the tunica intima and circular muscle bundles in the tunica media constructed an integrated power unit probably eliciting spontaneous lymph propulsion. Furthermore, the thoracic duct was richly supplied with blood vessels not only in the tunica externa, but also just beneath the endothelium. The present findings provide a morphological basis for investigation of human thoracic duct in basic and clinical medicine.

Communications
  • Shinhye LEE, Satoshi TSUZUKI, Takahiko AMITSUKA, Daisaku MASUDA, Shizu ...
    2017 年 38 巻 3 号 p. 207-213
    発行日: 2017/06/01
    公開日: 2017/06/20
    ジャーナル フリー

    Cluster of differentiation 36 (CD36) is a broadly expressed transmembrane receptor that has multiple ligands. It has been found to occur abundantly on the surface of the olfactory epithelium in mice and postulated to play a role in mammalian olfaction. However, there have been no ethological analyses of the mammalian behaviour showing CD36 involvement in the olfactory perception of a distinct odour-active volatile compound. In this study, we aimed to assess whether mammals perceive oleic aldehyde, an odour-active volatile that serves as a potential CD36 ligand, and if so, whether CD36 is involved in the sensing by following measurements using CD36-knockout mice and their wild-type littermates. In a two-bottle choice test, wild-type mice, but not CD36-knockout mice, discriminated a sucrose solution containing oleic aldehyde from the sucrose solution alone. To assess the importance of the olfactory system in the oleic aldehyde perception, we conducted an exploration test where the animals could rely primarily on the odour of test volatiles for recognition. We found that the wild-type, but not CD36-knockout mice, were aware of the compound. Our results provide behavioural evidence that CD36 plays a role in the perception of specific odour-active volatile compounds in the nasal cavity.

  • Daisuke TAKEI, Miyuki NISHI, So-ichiro FUKADA, Masao DOI, Hitoshi OKAM ...
    2017 年 38 巻 3 号 p. 215-219
    発行日: 2017/06/01
    公開日: 2017/06/20
    ジャーナル フリー

    The Gm7325 gene, bioinformatically identified in the mouse genome, encodes a small protein but has not been characterized until recently. Our gene expression analysis revealed that Gm7325 transcription is remarkably upregulated in injured skeletal muscle tissues. Activated satellite cells and immature myotubes were densely decorated with positive signals for Gm7325 mRNA in in situ hybridization analysis, while no obvious signals were observed in quiescent satellite cells and mature myofibers. In the 5’-flanking regions of mouse Gm7325 and its human homologue, conserved E-box motifs for helix-loop-helix transcription factors are repeatedly arranged around the putative promoter regions. Reporter gene assays suggested that MyoD, a master transcription factor for myogenesis, binds to the conserved E-box motifs to activate Gm7325 expression. Therefore, Gm7325, as a novel MyoD-target gene, is specifically induced in activated satellite cells, and may have an important role in skeletal myogenesis.

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