| 1.
論文 |
論文
|
Imaizumi, Tadaatsu ; Mori, Fumiaki ; Yagihashi, Norito ; Kitamura, Hideo ; Sashinami, Hiroshi ; Suzuki, Koichi ; Yamashita, Koji ; Taima, Kageaki ; Kubota, Kosei ; Tanji, Kunikazu ; Sakaki, Hirotaka ; Matsumiya, Tomoh ; Yoshida, Hidemi ; Mariya, Yasushi ; Nakane, Hajime ; Tanaka, Hiroshi ; Takanashi, Shingo ; Wakabayashi, Koichi ; Yagihashi, Soroku ; Nakane, Akio ; Ito, Etsuro ; Okumura, Ken ; Kimura, Hiroto ; Satoh, Kei
概要:
Retinoic acid-inducible gene-I （RIG-I） is a cytoplasmic protein regarded as putative RNA helicase.Immunohistochemical st
…
udies revealed high levels of RIG-I expression in epidermic cells in psoriasis, in macrophagesin atherosclerotic lesions and in glomeruli of lupus nephritis. RIG-I expression was also demonstrated in macrophagesand vascular endothelial cells in experimental animals with Listeria or Hanta virus infection. In vitro studies using cellcultures revealed the expression of RIG-I, in various cells including endothelial cells, macrophages and astroglial cells, inresponse to the stimulation with cytokines, lipopolysaccharide, double-stranded RNA, Listeria monocytogenes, etc. Thestudies employing the overexpression or RNA interference suggested that RIG-I is involved in the regulation of cytokineexpression including CXCL10/IP-10 and CCL5/RANTES. These results suggest that RIG-I constitutes a part of theintracellular pathway for the regulation of infl ammatory and immune responses.
続きを見る
|
||||
| 2.
論文 |
論文
|
Kijima, Hiroshi ; Sato, Fuyuki ; Bhawal, Ujjal Kumar ; Kawamoto, Takeshi ; Fujimoto, Katsumi ; Imaizumi, Tadaatsu ; Imanaka, Tadanobu ; Kondo, Jun ; Koyanagi, Satoru ; Noshiro, Mitsuhide ; Yoshida, Hidemi ; Kato, Yukio
概要:
The circadian rhythms in mammals are regulated by a pacemaker located in the suprachiasmatic nucleus of the hypothalamus
…
. Five clock-gene families, i.e. Clock, Bmal, Per, Cry and Dec, have been found to be involved in a transcription-translation feedback loop that generates the circadian rhythm at the intracellular level. In this study, we examined functional analysis of the Dec gene. DEC1 and DEC2 are basic-helix-loop-helix （bHLH） transcription factors, involved in cellular diff erentiation, responses to hypoxia, and circadian rhythms. We recently showed that the expression of DEC1 and DEC2 was upregulated by hypoxia, however, the functions of these two factors under hypoxic conditions have not been elucidated in detail. It is well established that the expression of vascular endothelial growth factor （VEGF） is upregulated by hypoxia, and the expression of VEGF in response to hypoxia depends on transcriptional activation by a heterodimer comprising hypoxia-inducible factor 1 α （HIF-1α） and arylhydrocarbon receptor nuclear translocator 1 （ARNT1）. In the present study, we showed that DEC2, but not DEC1, suppressed VEGF gene expression under hypoxic conditions. DEC2 protein was co-immunoprecipitated with HIF-1α but not with ARNT1. The binding of HIF-1α to the hypoxia response element（ HRE） in the VEGF promoter was decreased by DEC2 overexpression, and increased by DEC2 knockdown. We also showed that the circadian expression of VEGF showed a reciprocal pattern to that of DEC2 in cartilage. DEC2 had a circadian oscillation in implanted Sarcoma 180 cells. We conclude that DEC2 negatively regulates VEGF expression and plays an important role in the pathological conditions in which VEGF is involved.
続きを見る
|
||||
| 3.
論文 |
論文
|
Yoshida, Hidemi ; Mimura, Junsei ; Imaizumi, Tadaatsu ; Matsumiya, Tomoh ; Ishikawa, Akira ; Metoki, Norifumi ; Tanji, Kunikazu ; Ota, Ken ; Kosaka, Kunio ; Itoh, Ken ; Satoh, Kei
概要:
Optimization of neuronal function and survival is an important goal in the treatment of cerebrovascular diseases in orde
…
r to avoid or improve devastating long-term sequelae. Nerve growth factor （NGF） is essential for neuronal growth and survival in the central nervous system （CNS）. Vascular endothelial growth factor （VEGF） is a potent mitogen specifi c for endothelial cells and a stimulator of neovascularization. VEGF also enhances vascular permeability, which may promote the development of brain edema during cerebral ischemia. These molecules aff ect the outcome of ischemia/reperfusion injury in the CNS. Edaravone, a brain-penetrant, free radical scavenger, is known to ameliorate postischemic neuronal dysfunction. Transcription factor Nrf2（ nuclear factor-erythroid 2-related factor 2）, a master regulator of antioxidant responses, plays an important role in the coordinated expressions of stress-inducible genes. Astrocytes express various genes involved in the regulation of neuronal functions, and the regulation of astrocyte gene expressions may be a potential therapeutic target in brain injury. This review aims to appraise the eff ects of radical scavenger edaravone and a natural Nrf2-inducer as neuroprotective agents in human astrocytes, particularly under an experimental model for hypoxia/reoxygenation.
続きを見る
|
||||
| 4.
論文 |
論文
|
Imaizumi, Tadaatsu ; Aizawa, Tomomi ; Tanaka, Hiroshi ; Sato, Fuyuki ; Xing, Fei ; Matsumiya, Tomoh ; Yoshida, Hidemi ; Satoh, Kei
概要:
Viral infection is important in renal pathology both as a trigger of chronic inflammatory diseases and as a complicatio
…
n associated with organ transplantation. Glomerular mesangial cells produce a variety of functional molecules potentially involved in immune reactions, and we investigated anti-viral responses in normal human mesangial cells. Human mesangial cells were treated with polyinosinic-polycytidylic acid （poly IC）, an authentic double-stranded RNA that mimics viral RNA. Treatment of cells with poly IC induced interferon-β （IFN-β）, retinoic acid-inducible gene-I（ RIG-I）, CC chemokine ligand 5（ CCL5）, differentiated embryo-chondrocyte 2（ DEC2） and IFN-stimulated gene 20 （ISG20）. Knockdown of toll-like receptor 3 （TLR3）, by RNA interference （RNAi）, abolished the poly IC-induced expression of these molecules. RNAi against IFN-β inhibited the induction of RIG-I,CCL5 and ISG20, but not of DEC2. Knockdown of RIG-I resulted in the reduced expression of CCL5. RNAi against DEC2 enhanced the poly IC-induced expression of IFN-β, RIG-I and CCL5. Transfection of cells with a poly IC/cationic lipid complex induced IFN-β, RIG-I and ISG20. Knockdown of RIG-I decreased the expression of IFN-β and ISG20 induced by transfection with poly IC/cationic lipid. TLR3 and RIG-I may function as recognition receptors against double-stranded RNA, which induce IFN-β and its downstream IFN-inducible genes. In the signaling elicited by poly IC, the IFN-inducible genes include RIG-I and effector molecules as CCL5 with leukocyte chemotactic activity and ISG20 with exonuclease activity on single-stranded RNA. The poly IC-induced expression of DEC2 is independent on IFN-β and it may control the signaling elicited by double-stranded RNA. The poly IC-inducible molecules may mediate anti-viral innate responses in renal mesangial cells.
続きを見る
|
||||
| 5.
論文 |
論文
|
Narita, Norihiko ; Matsumiya, Tomoh ; Kon, Takao ; Hayakari, Ryo ; Itoh, Ryohei ; Kubota, Kosei ; Sakaki, Hirotaka ; Furudate, Ken ; Yoshida, Hidemi ; Imaizumi, Tadaatsu ; Kobayashi, Wataru ; Kimura, Hiroto
概要:
The CXC chemokine growth-related oncogene protein-α （GRO-α） has a wide variety of biological activities including as neu
…
trophil trafficking or migration of vascular endothelial cells. In addition, studies have shown a crosstalk between tumor cells and vascular endothelial cells; GRO-α released by endothelial cells induces invasion of tumor cells toward endothelial cells, indicating an importance of GRO-α in a tumor environment. Oral squamous cells are reported to produce GRO-α in response to cytokines such as tumor necrosis factor-α （TNF-α）. However, little is known about how GRO-α is involved in oral cancer. Here, we investigated the biological role of GRO-α for both tumor growth and angiogenesis in oral squamous cell carcinoma cells. We first evaluated the effect of TNF-α on GRO-α expression in three oral cancer cells from different origins. Among the cell lines we used, KOSC-2 cells expressed the highest amount of GRO-α mRNA in response to TNF-α. TNF-α-treated condition medium from KOSC-2 cells enhanced endothelial cell chemotaxis and the chemotactic activity was partially inhibited by the addition of neutralizing anti-GRO-α antibody. In addition, GRO-α exerted tumor cell migration of KOSC-2. From these results, we conclude that GRO-α may contribute to both angiogenesis and proliferation in oral cancer.
続きを見る
|
||||
| 6.
論文 |
論文
|
Shintaku, Tomohiro ; Ohba, Takayoshi ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Hirota, Kazuyoshi ; Ono, Kyoichi ; Mariya, Yasushi ; Imaizumi, Tadaatsu ; Sawamura, Daisuke ; Murakami, Manabu
概要:
General anesthesia is important for pharmacological studies in laboratory animals. Although a number of transgenic anima
…
ls have been reported, basic analyses concerning mouse ECG and heart rate variability（ HRV） have not been rigorously examined.
続きを見る
|
||||
| 7.
論文 |
論文
|
Shintaku, Tomohiro ; Ohba, Takayoshi ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Hirota, Kazuyoshi ; Ono, Kyoichi ; Mariya, Yasushi ; Imaizumi, Tadaatsu ; Sawamura, Daisuke ; Murakami, Manabu
概要:
We compared the effects of inhalation anesthesia（ 2% isoflurane）, intraperitoneal injection of pentobarbital anesthesia
…
（50 mg/kg）, and a combination anesthetic consisting of medetomidine, midazolam and butorphanol （MMB） on electrocardiograms in mice. Using either isoflurane inhalation anesthesia or pentobarbital anesthesia, heart rate （HR） was in the acceptable range （ca. 450-500 bpm）. In contrast, MMB anesthesia decreased HR significantly. Importantly, MMB anesthesia responded minimally to propranolol （β-blocker）, suggesting that MMB anesthesia affects sympathetic tonus and is not suitable for evaluation of the cardiovascular or sympathetic system. We confirmed that modified MMB, with a decreased dose of medetomidine from the original protocol（ an α2 agonist）, was associated with a HR of 400 bpm and a diminished response to propranolol. Our present results illustrate the importance of using an appropriate form of anesthesia suitable for experimental pharmacological studies.
続きを見る
|
||||
| 8.
論文 |
論文
|
Onda, Kaoru ; Yoshida, Hidemi ; Hayakari, Ryo ; Xing, Fei ; Wang, Lian ; Matsumiya, Tomoh ; Kawaguchi, Shogo ; Murakami, Manabu ; Imaizumi, Tadaatsu
概要:
Dysregulation of iron homeostasis in brain causes various neurodegenerative disorders. In fact, high concentration of ir
…
on is present in brains of patients with Alzheimer’s disease. It was previously reported that CXCL8 protects human neurons from amyloid-β-induced neurotoxicity and that astrocytes have the potential to play important roles in Alzheimer’s disease. In the present study, we examined the effect of desferrioxamine, an iron chelator, on the expression of CXCL8 in U373MG human astrocytoma cells used as a model of astrocytes. Treatment of the cells with desferrioxamine induced the expression of CXCL8. Pretreatment of the cells with FeSO4 counteracted the positive effect of desferrioxamine on CXCL8 production, suggesting that the effect of desferrioxamine was due to iron chelation. RNA interference experiments showed that HIF-1α was not involved in desferrioxamine-induced CXCL8 expression. We conclude that desferrioxamine induces CXCL8 in astrocytes and the chelation of iron may be a new therapeutic strategy for Alzheimer’s disease.
続きを見る
|
||||
| 9.
論文 |
論文
|
Furudate, Ken ; Matsumiya, Tomoh ; Hayakari, Ryo ; Xing, Fei ; Kubota, Kosei ; Sakaki, Hirotaka ; Tamura, Yoshihiro ; Kijima, Hiroshi ; Imaizumi, Tadaatsu ; Kimura, Hiroto ; Kobayashi, Wataru
概要:
Tumor microenvironment is related to growth, survival, invasion, and metastasis of tumor cells. Several studies have pro
…
ved that stromal fibroblasts play an important role in the tumor microenvironment to convert cancer-associated fibroblast （CAFs）. Clock genes are known to regulate circadian rhythms, angiogenesis, and immunoreaction. In addition, clock genes play an important role in cancer development. However, little has been shown about how these clock genes function in the tumor microenvironment. In the present study, we investigated to evaluate the effect of co-culture fibroblasts with oral cancer cells on the expression of clock genes. Following the coculture of human primary fibroblasts with human gingival carcinoma Ca9-22 cells, the expression levels of clock genes were analyzed by real-time quantitative PCR. We found that the rhythmic expression of clock genes were altered, enhanced, or disappeared by the co-culture. Such effect was observed not only in fibroblasts in the presence of Ca9-22 cells but also in Ca9-22 cells in the presence of fibroblasts. Our results suggested that clock genes might affect an important role in the tumor microenvironment.
続きを見る
|
||||
| 10.
論文 |
論文
|
Chong, Han ; Ogata, Yoshiki ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Watanabe, Hiroyuki ; Imaizumi, Tadaatsu ; Hirota, Kazuyoshi ; Ono, Kyoichi ; Ohba, Takayoshi ; Murakami, Manabu
概要:
Transgenic mice experiments have become increasingly popular to research human inherited disease.However, a number of Ja
…
panese researchers have difficulty with the selection of anesthesia, after the classificationof ketamine, probably the most used anesthesia, as a narcotic drug in 2006. Therefore, we compared the effects ofinhalation anesthesia （2% of isoflurane, sevoflurane and enflurane） and intraperitoneal pentobarbital anesthesia （50mg/kg） on the electrocardiogram（ ECG） and blood oxygen saturation（ SPO2） of mice. With inhalation anesthesia, theheart rate（ HR） and SPO2 were within an acceptable range. In contrast, the HR significantly decreased after initiationof pentobarbital anesthesia, and gradually returned to a low rate. Importantly, pentobarbital anesthesia significantlylowered SPO2, and heart rate variability analysis showed unstable beat-to-beat intervals during pentobarbitalanesthesia, suggesting that inhalation anesthesia is more suitable for evaluation of cardiorespiratory responsesthan pentobarbital anesthesia. During anesthesia, propranolol, a ????-adrenergic blocker, significantly decreased heartrate. Atropine, a parasympathetic blocker, also significantly increased heart rate. Our data suggest that inhalation anesthesia is suitable for cardiorespiratory analysis in mice.
続きを見る
|
||||
| 11.
論文 |
論文
|
Nozaki, Shuhei ; Ogata, Yoshiki ; Yonekura, Manabu ; Han, Chong ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Hirota, Kazuyoshi ; Matsuzaki, Yasushi ; Tomita, Hirofumi ; Imaizumi, Tadaatsu ; Itagaki, Shirou ; Sawamura, Daisuke ; Murakami, Manabu
概要:
We analyzed the effects of halothane as an inhalational anesthetic agent on electrocardiogram （ECG）parameters in C57/BL6
…
mice. Following induction of anesthesia using 2% halothane, the ECGs showed a regularpattern and the heart rate （HR） was within an acceptable range （~500 bpm）. The HR decreased with increasinghalothane concentration in a concentration-dependent fashion. The frequency domain analysis showed that the high-frequency （HF） component decreased and the lowfrequency（LF） component increased in a concentration-dependent fashion. Therefore, the LF/HF ratio increasedwith increasing halothane concentration, suggesting effects on the autonomic nervous system. We analyzed the pharmacological response to sympathetic blockade with propranolol, a typical adrenergicβ-blocker, under halothane anesthesia. Propranolol administration resulted in a decreased HR; interestingly,intraperitoneal injection of propranolol （120 μg/kg body weight） resulted in arrhythmia （sick sinus syndrome）during anesthesia with 3% halothane. Our results indicate the importance of selecting a suitable anesthetic agent for C57/BL6 mice in pharmacological studies
続きを見る
|
||||
| 12.
論文 |
論文
|
Ogata, Yoshiki ; Yonekura, Manabu ; Yamaki, Rouichi ; Han, Chong ; Fujiwara, Tomonori ; Seya, Kazuhiko ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Imaizumi, Tadaatsu ; Hirota, Kazuyoshi ; Tomita, Hirofumi ; Murakami, Manabu
概要:
We examined the effects of enflurane anesthesia on the mouse cardiac autonomic nervous system usingelectrocardiogram（ EC
…
G） analysis. Enflurane had a lower effect on heart rate（ HR） compared to isoflurane, which ismore widely used in small animal studies. Under anesthesia with 3 or 4% of enflurane, administration of propranololhad a significant effect on HR. Enflurane increased R-R interval length in a dose-dependent fashion, and the R-Rinterval became unstable at high concentrations. Although HR decreased with high doses of enflurane, we observednormal sinus rhythm and no arrhythmia. These results suggest that the effect of enflurane anesthesia is acceptableeven though the drug can lead to cardiac instability. No remarkable changes were observed in HR frequency. These results suggest that enflurane anesthesia may be suitable for cardiac autonomic nervous system analysis.
続きを見る
|
||||
| 13.
論文 |
論文
|
Seya, Kazuhiko ; Motomura, Shigeru ; Imaizumi, Tadaatsu ; Furukawa, Ken-Ichi
概要:
Two sensitive enzymatic fluorometric assays have been developed for adenosine 3’,5’-cyclic monophosphate（cAMP） by Sugiya
…
ma et al. （Anal. Biochem. 1990） and for guanosine 3’,5’-cyclic monophosphate （cGMP） by Seyaet al. （Anal. Biochem. 1998）. However, to make a new simultaneous comparison of two cyclic nucleotides, distinctmeasurement methods cause less reliability and longer measurement time. To overcome these problems, wedeveloped a simultaneous measurement method for them. All adenosine nucleotides and GMP were enzymaticallydegraded using alkaline phosphatase and apyrase. The remaining GDP was converted to GTP by creatine kinase.Cyclic GMP and cAMP, absorbed into a Sep-Pak amino propyl cartridge, were eluted to separate from GTP, andthen were simultaneously quantified using improved enzymatic fluorometric assay. The detection limits for cAMPand cGMP were 1 and 5 fmol, respectively. The total measurement time was about 10 h. Using this method, thebasal cAMP and cGMP levels in rat aortic smooth muscle cells were confirmed to 4.1 and 0.042 pmol/mg protein,respectively. An adrenergic agonist, isoproterenol （1 μM） increased cAMP approximately 6 fold, while nitric oxidedonor, S-nitroso-N-acetylpenicillamine （100 μM） increased cGMP approximately 230 fold. These results suggest thatthis simultaneous measurement of cGMP and cAMP can provide a more convenient assessment of them in biological samples.
続きを見る
|
||||
| 14.
論文 |
論文
|
Imaizumi, Tadaatsu ; Hayakari, Ryo ; Watanabe, Shojiro ; Aizawa, Tomomi ; Matsumiya, Tomoh ; Yoshida, Hidemi ; Tsuruga, Kazushi ; Kawaguchi, Shogo ; Tanaka, Hiroshi
概要:
Cylindromatosis (CYLD), a deubiquitinase, negatively regulates nuclear factor-κB in various cells. However, its potentia
…
l roles in glomerular inflammation remain unclear. Because the activation of the Toll-like receptor 3 (TLR3)/type I interferon (IFN) pathways plays a pivotal role in chronic kidney diseases (CKD), we examined the role of CYLD in the TLR3 signaling in cultured human mesangial cells (MCs).<br />We stimulated CYLD-silenced MCs with polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of dsRNA, and studied representative TLR3/IFN-β pathways (i.e., TLR3/IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5, and TLR3/IFN-β/melanoma differentiation associated gene 5 (MDA5)/CXCL10 axes) using RT-PCR, western blotting, and ELISA. We also used immunofluorescence staining and microscopy to examine mesangial CYLD expression in biopsied specimens from patients with CKD.<br />CYLD silencing resulted in an increase of poly IC-induced RIG-I and MDA5 protein levels and increased CCL5 and CXCL10 mRNA and protein expression, but unexpectedly decreased mRNA expressions of RIG-I and MDA5. Interestingly, CYLD silencing did not affect IFN-β or the phosphorylated STAT1 (signal transducers and activator of transcription protein 1). CYLD was highly expressed in biopsied specimens from patients with proliferative lupus nephritis (LN).<br />CYLD inhibits post-transcriptional regulation of RIG-I and MDA5 expression following TLR3 activation in MCs. CYLD may be involved in the pathogenesis of CKD, especially pathogenesis of LN.
続きを見る
|
||||
| 15.
論文 |
論文
|
Tanaka, Hiroshi ; Imaizumi, Tadaatsu
概要:
The innate and adaptive immune systems have been reported to play an important role in the pathogenesis of glomerular diseases. Since viral infections may trigger the development of inflammatory renal disease or the worsening of
…
preexisting renal disease, recent studies have focused on the involvement of toll-like receptors (TLRs) and their signaling pathways in the inflammatory processes of glomerular cells. Viral double-stranded RNA (dsRNA) can activate not only TLR3 located within intracellular endosomes but also retinoic-acid-inducible-gene-I- (RIG-I-) like helicase receptors located within the cytosol. RIG-I and melanoma differentiation-associated gene 5 (MDA5) are members of the RNA helicase family in the cytosol, and both act as pathogen recognition receptors. The activation of TLRs and their downstream immune responses can be induced by both infectious pathogens and noninfectious stimuli such as endogenous ligands, and this mechanism may be involved in the pathogenesis of autoimmune renal diseases. However, there are few data on the interaction between TLR3, MDA5, and RIG-I in autoimmune glomerular diseases. Based on our recent experimental studies using cultured normal human mesangial cells (MCs), we found that novel TLR3-mediated signaling pathways in MCs may be involved in the pathogenesis of glomerular diseases. In the present paper, we summarize our recent findings.
続きを見る
|
||||
| 16.
論文 |
論文
|
Imaizumi, Tadaatsu ; Yano, Chikashi ; Numata, Akiko ; Tsugawa, Koji ; Hayakari, Ryo ; Matsumiya, Tomoh ; Yoshida, Hidemi ; Watanabe, Shojiro ; Tsuruga, Kazushi ; Kawaguchi, Shogo ; Murakami, Manabu ; Tanaka, Hiroshi
概要:
Activation of Toll-like receptor 3 (TLR3) signaling followed by type I interferon (IFN) expression is crucial in antivir
…
al and "pseudoviral" immune reactions in renal mesangial cells (MCs). These reactions are probably involved in the pathogenesis of chronic kidney disease (CKD). However, the role of IFN-induced 35-kDa protein 35 (IFI35), a type I IFN-dependent transcript, in glomerular inflammation is unclear. Here, we aimed to investigate the expression and the role of IFI35 in IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5 and IFN-β/melanoma differentiation-associated gene 5 (MDA5)/CXCL10 axes in MCs.<br />We treated human MCs with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, then analysed the IFI35 expression by reverse transcription-polymerase chain reaction and western blotting. To examine the regulation of IFI35 expression, we subjected MCs to RNA interference (siRNA) against IFN-β, RIG-I, and MDA5.<br />Activation of TLR3 by poly IC induces the IFI35 expression in MCs. siRNA against IFN-β inhibited poly IC-induced IFI35 expression. Knockdown of IFI35 resulted in a decrease of poly IC-induced RIG-I and MDA5 protein as well as decreased CCL5 and CXCL10 mRNA and protein expression. However, it did not affect the expression of none of phosphorylated signal transducers or activator of transcription (STAT) 1 protein, or RIG-I and MDA5 in mRNA levels.<br />Regional expression of IFI35 and its dysregulation may be involved in the pathogenesis of glomerular inflammation in CKD.
続きを見る
|
||||
| 17.
論文 |
論文
|
Aizawa, Tomomi ; Imaizumi, Tadaatsu ; Tsuruga, Kazushi ; Watanabe, Shojiro ; Yoshida, Hidemi ; Kumagai, Naonori ; Ito, Etsuro ; Tanaka, Hiroshi
概要:
Renal biopsy is the gold standard for confirmation of disease severity and diagnosis of glomerulonephritis (GN), but its procedure is invasive with a risk of complications. Thus, a non-invasive monitoring method is desirable especially
…
in pediatric patients. Fractalkine and monocyte chemoattractant protein-1 (MCP-1) are proinflammatory chemokines, and both have been reported to be involved in the pathogenesis of immunocomplex-mediated GN. Recently, it has been reported that urinary fractalkine and MCP-1 may serve as possible predictors of disease activity of adult patients with GN. We, therefore, examined whether urinary levels of fractalkine and MCP-1 correlate with clinical and histologic parameters. Twenty-six consecutive children with various types of GN were enrolled in this study, including lupus nephritis, IgA nephropathy, membranous nephropathy, acute GN, and thin basement membrane disease (served as a non-inflammatory control). Urinary fractalkine and MCP-1 concentrations in the first morning urine samples obtained at the time of renal biopsy were measured by enzyme-linked immunosorbent assay, and standardized for urinary creatinine concentrations. Urinary fractalkine concentration differed significantly among the disease categories. Urinary concentrations of fractalkine and MCP-1 showed a significant positive correlation with the degree of occult blood in urine and a significant inverse correlation with the estimated glomerular filtration rate. Furthermore, the urinary MCP-1 concentration was significantly correlated with histological chronicity indices in patients with lupus nephritis and IgA nephropathy. Measurement of urinary fractalkine and MCP-1 concentrations may be useful as a non-invasive method for predicting the disease activity of GN in children.
続きを見る
|
||||
| 18.
論文 |
論文
|
Kimura, Toshiro ; Imaizumi, Tadaatsu ; Yoshida, Tatsuya ; Shimada, Taku ; Hayakari, Ryo ; Kawaguchi, Shogo ; Yoshida, Hidemi ; Kobayashi, Tamotsu ; Hirabayashi, Takeshi ; Mizukami, Hiroki ; Kijima, Hiroshi ; Hakamada, Kenichi
概要:
Purpose: Retinoic acid-inducible gene-I （RIG-I） is a member of cytoplasmic viral sensors which plays an important role i
…
n inflammation of biliary epithelial cells（ BECs）. The aim of this study is to examine if RIG-I and C-X-C motif chemokine 10（ CXCL10） are involved in the etiology of human biliary atresia（ BA）.Methods: Immunohistochemical study was performed on surgically resected tissues obtained（ June 1994 to March 2016）from 30 infants with BA and non-inflamed hepatic tissues from 7 infants with hepatoblastoma. A semiquantitative scoring system was designed to evaluate the staining with an antibodies to the RIG-I and CXCL10. The expression of RIG-I and CXCL10 in HuCCT1 cholangiocarcinoma cell line were studied by western blotting, ELISA and RT-PCR analyses.Results: Intense immunoreactivity for RIG-I and CXCL10 was detected in BECs in tissues resected from BA patients.The expression of RIG-I and CXCL10 in the hilar tissue was significantly stronger than in the hepatic tissue.Transfection of HuCCT1 cells with poly（I:C）, a synthetic analog of viral dsRNA, induced the expression of RIG-I, and knockdown of RIG-I inhibited the induction of CXCL10 in HuCCT1 cells transfected with poly（I:C）.Conclusion: These results suggest that RIG-I-CXCL10 cascade may be involved in the etiology of human BA.
続きを見る
|
||||
| 19.
論文 |
論文
|
Yoshida, Hidemi ; Hashimoto, Yuko ; Fukushima, Takashi ; Tanji, Kunikazu ; Matsumiya, Tomoh ; Seya, Kazuhiko ; Kawaguchi, Shogo ; Imaizumi, Tadaatsu
概要:
Toxic amyloid-beta （Aβ） is known to generate symptoms of Alzheimer’s disease （AD）; however, less is known regarding the
…
neurotoxicity of Aβ at lower concentrations. Moreover, the neuroprotective potential of combination treatment with plant biophenols and existing drugs is not well understood. In this study, we estimated the no-observed adverse effect level （NOAEL） of Aβ 1–42 （Aβ42） against cultured human neuroblastoma SHSY5Y cells, and examined the neuroprotective effect of combination pretreatment with 10 μM carnosic acid, 30 nM rebamipide, 10 μM edaravone, and 10 μM of resveratrol （the “CRER” blend） on weak but toxic Aβ42-treated SH-SY5Y cells. We evaluated the NOAEL of Aβ42 at 500 nM in these cells. Aβ42 at 1–8 μM reduced cell viability; however, the “CRER” blend ameliorated this Aβ42-induced decrease in viability. The “CRER” blend induced the expression of Aβ-degrading enzymes including matrix metalloproteinase-14 （MMP-14） and neprilysin, while also enhancing the expression of the inducible α-secretase TACE （tumor necrosis factor-α-converting enzyme）, sirtuin 1 （SIRT1）, and brain-derived neurotrophic factor（ BDNF）. Collectively, our results indicate that the “CRER” may aid in the prevention of Aβ toxicity by enhancing MMP-14, neprilysin, TACE, SIRT1, and BDNF. Thus, the “CRER” blend may prove to be a promising strategy for the prevention of Aβ-mediated disorders, particularly AD.
続きを見る
|
||||
| 20.
論文 |
論文
|
Yu, Zaiqiang ; Daitoku, Kazuyuki ; Fukuda, Ikuo ; Imaizumi, Tadaatsu ; Minakawa, Masahito ; Furukawa, Ken-Ichi ; Seya, Kazuhiko
概要:
Objective: Wingless/integrase 5a（Wnt5a） pathway is known to regulate the osteogenesis. In this study, we aimed to clarif
…
y the role of Wnt5a pathway in aortic valve ectopic calcification.Methods: Human aortic valve interstitial cells（HAVICs） were obtained from calcified aortic valves of patients with calcific aortic valve stenosis（CAVS）. HAVICs were separated to CD34-negative and -positive cells by flow cytometry. We measured real-time PCR, alkaline phosphatase（ALP） activity, Alizarin Red S staining as an index of calcification. Immunohistochemical staining was performed to confirm the distribution of Wnt5a on calcified and normal aortic valves.Results: HAVICs, especially, CD34-negative cells are highly sensitive to tumor necrosis factor-α（ TNF-α, 30 ng/mL）, and which accelerated the Wnt5a gene expression. Wnt5a antagonist, box5, did not down-regulate HAVIC calcification induced by TNF-α. Further, Wnt5a agonist, foxy5, did not accelerated HAVIC calcification induced by TNF-α. There was no significant difference in the TNF-α-induced acceleration of ALP activity between the cells treated with foxy5 and box5. Furthermore, the proportion of Wnt5a positive cells was no difference between calcified and normal valves.Conclusions: We confirmed that Wnt5a pathway does not regulate the TNF-α-induced aortic valve calcification in HAVICs obtained from CAVS patients.
続きを見る
|
||||
| 21.
論文 |
論文
|
Akiyama, Natsumi ; Kubota, Kosei ; Komatsu, Shotaro ; Itoh, Ryohei ; Chang, Hao Chi ; Yamazaki, Shunya ; Imaizumi, Tadaatsu ; Matsumiya, Tomoh ; Kobayashi, Wataru
概要:
Objective: Medication-related osteonecrosis of the jaw （MRONJ） is a complication of bisphosphonate （BP） therapy. The pat
…
hophysiology of MRONJ remains unclear. Extensive studies have been performed to examine the effect of BPs on bone metabolism. Breakdown of mucosa is a factor classified into five stages in MRONJ, indicating an important role of oral soft tissue in the pathogenesis of MRONJ.Methods: We investigated the effect of alendronate, one of the most commonly used BPs worldwide, on the proliferation of human gingival fibroblasts by MTT assay, western blotting, and wound healing assay.Results: We observed time- and concentration-dependent inhibition of fibroblast proliferation by alendronate. Wound healing assays also showed that alendronate prolonged wound healing in a concentration-dependent manner. MAP kinase signaling pathway exhibits a cardinal role in cell proliferation; however, little is known about whether BPs affect classical MAP kinase ERK in fibroblasts. We found that U0126, a selective inhibitor of MAP kinase kinase （MEK1/2）, inhibited fibroblast proliferation similarly to alendronate. Alendronate was also found to inactivate ERK1/2, both of which are downstream molecules of MEK1/2.Conclusion: our findings indicated that alendronate inhibits the proliferation of human gingival fibroblasts via inactivation of ERK1/2.
続きを見る
|
