Curriculum Vitaes

Muroi Masashi

  (室井 正志)

Profile Information

Affiliation
Faculty of Pharmacy Department of Pharmaceutical Sciences, Musashino University
Degree
博士(国立富山医科薬科大学)

J-GLOBAL ID
200901062330622699
researchmap Member ID
0000050848

Research History

 6

Papers

 32
  • Tomoya Narita, Yusuke Murakami, Takashi Isii, Masashi Muroi, Naomi Yamashita
    Journal of Leukocyte Biology, Dec 30, 2023  Peer-reviewed
    Abstract Eosinophils are typical effector cells associated with type 2 immune responses and play key roles in the pathogenesis of allergic diseases. These cells are activated by various stimuli, such as cytokines, chemokines, and growth factors, but the regulatory mechanisms of eosinophil effector functions remain unclear. Glucocorticoid-induced TNF receptor family-related protein (GITR), a transmembrane protein belonging to the TNF receptor superfamily, is a well-known regulatory molecule for T cell activation. Here, we show that GITR is also constitutively expressed on eosinophils and functions as a co-stimulatory molecule for these cells. Although degranulation was unaffected by GITR engagement of murine bone marrow-derived eosinophils (bmEos), secretion of inflammatory cytokines such as interleukin (IL)-4, IL-6, and IL-13 from IL-33-activated bmEos were augmented by anti-mouse GITR agonistic antibody (DTA-1). In conclusion, our results provide a new regulatory pathway of cytokine secretion from eosinophils where GITR functions as a co-stimulatory molecule.
  • Sachiko Watanabe, Kosuke Zenke, Masashi Muroi
    The Journal of Immunology, Mar 10, 2023  Peer-reviewed
    Abstract LPS interacts with TLR4, which play important roles in host-against-pathogen immune responses, by binding to MD-2 and inducing an inflammatory response. In this study, to our knowledge, we found a novel function of lipoteichoic acid (LTA), a TLR2 ligand, that involves suppression of TLR4-mediated signaling independently of TLR2 under serum-free conditions. LTA inhibited NF-κB activation induced by LPS or a synthetic lipid A in a noncompetitive manner in human embryonic kidney 293 cells expressing CD14, TLR4, and MD-2. This inhibition was abrogated by addition of serum or albumin. LTAs from different bacterial sources also inhibited NF-κB activation, although LTA from Enterococcus hirae had essentially no TLR2-mediated NF-κB activation. The TLR2 ligands tripalmitoyl-Cys-Ser-Lys-Lys-Lys-Lys (Pam3CSK4) and macrophage-activating lipopeptide-2 (MALP-2) did not affect the TLR4-mediated NF-κB activation. In bone marrow–derived macrophages from TLR2−/− mice, LTA inhibited LPS-induced IκB-α phosphorylation and production of TNF, CXCL1/KC, RANTES, and IFN-β without affecting cell surface expression of TLR4. LTA did not suppress IL-1β–induced NF-κB activation mediated through signaling pathways shared with TLRs. LTAs including E. hirae LTA, but not LPS, induced association of TLR4/MD-2 complexes, which was suppressed by serum. LTA also increased association of MD-2, but not TLR4 molecules. These results demonstrate that, under serum-free conditions, LTA induces association of MD-2 molecules to promote formation of an inactive TLR4/MD-2 complex dimer that in turn prevents TLR4-mediated signaling. The presence of LTA that poorly induces TLR2-mediated activation but inhibits TLR4 signaling provides insight into the role of Gram-positive bacteria in suppressing inflammation induced by Gram-negative bacteria in organs such as the intestines where serum is absent.
  • Sachiko Watanabe, Kosuke Zenke, Yuka Sugiura, Masashi Muroi
    Immunobiology, 227(5) 152256-152256, Sep, 2022  Peer-reviewed
    Excessive activation of Toll-like receptor (TLR) leads to sepsis. Inflammatory responses to various microbiological components are initiated via different TLR proteins, but all TLR signals are transmitted by TRAF6. We reported that TRAF6 associated with ubiquitinated IRAK-1 undergoes proteasome-mediated degradation, suggesting that IRAK-1 has a negative regulatory role in TLR signaling. Here, we investigated the minimal structural region of IRAK-1 needed for degradation of TRAF6. The IRAK-1 protein contains an N-terminal death domain (DD; amino acids 1-102), a serine/proline/threonine-rich ProST domain (amino acids 103-197), a central kinase domain with an activation loop (amino acids 198-522), and the C-terminal C1 and C2 domains (amino acids 523-712), which contain two and one putative TRAF6-binding (TB) sites, respectively. TRAF6 degradation was severely impaired by deletion of the DD or C1 domain, and a mutant (DC1) containing only the DD and C1 domains could induce TRAF6 degradation. IRAK-1 mutants lacking the N- or C-terminal amino acids of DD induced little degradation. Deletion or mutation of TB2 (amino acids 585-591) in the C1 domain also inhibited TRAF6 degradation. An IRAK-1 mutant possessing only DD and TB2 did not induce TRAF6 degradation, although a mutant in which a short spacer was inserted between DD and TB2 induced TRAF6 degradation, which and DC1-induced degradation were inhibited by proteasome inhibitors. All IRAK-1 mutants that induced TRAF6 degradation could be immunoprecipitated with TRAF6. Meanwhile, NF-κB activation was observed for all IRAK-1 mutants-including those that failed to induce degradation and was severely impaired only for a mutant carrying mutations in both TBs of C1. These results demonstrate that only DD and TB2 separated by an appropriate distance can induce TRAF6 degradation. Conformational analysis of this minimal structural unit may aid development of low molecular compounds that negatively regulate TLR signaling.
  • Takashi Ishii, Masashi Muroi, Kazuhide Horiguchi, Ken-Ichi Tanamoto, Takahide Nagase, Naomi Yamashita
    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 49(12) 1624-1632, Dec, 2019  Peer-reviewed
    BACKGROUND: Type 2 innate lymphoid cells (ILC2s) are one of the sources of IL-5 and IL-13 in allergic airway inflammation. Innate immune receptors such as Toll-like receptors (TLRs) expressed on epithelial cells could contribute to ILC2 activation through IL-33 production, but a direct effect of TLRs on ILC2s remains to be elucidated. OBJECTIVES: We hypothesized that TLRs can directly activate lung ILC2s and participate in the pathogenesis of asthma. METHODS: After intranasal administration of IL-33 to wild-type (WT), TLR2KO and TLR4KO female mice, ILC2s were isolated from harvested lungs. ILC2s were incubated with IL-2 and TLR stimulants (pam3csk4 (PAM), house dust mite extract (HDM)). In some experiments, TLR2 or dectin-1 signalling inhibitors were used. As an in vivo model, the mice were treated with IL-33 and rested until lung recruitment of eosinophils regressed. Then they were treated intranasally with PAM + HDM or vehicle and analysed. RESULTS: In vitro stimulation of isolated ILC2s showed that PAM could induce IL-13 and IL-5 production, and HDM had a synergistic effect on this stimulation. Both effects were dependent on TLR2 and NF-κB signalling. PAM + HDM stimulation of WT mice led to increased ILC2s, airway hyperresponsiveness and increased levels of both neutrophils and eosinophils in bronchoalveolar lavage fluid. These observations were dependent on TLR2. CONCLUSIONS & CLINICAL RELEVANCE: TLR2 can directly activate lung ILC2s, an effect that is augmented by HDM. Asthmatic characteristics mediated through the TLR2 pathway were evident in the in vivo mice model. These data implicate a new pathway of ILC2 activation in the pathogenesis of asthma.
  • Masashi Muroi, Norihiko Ogura, Hikaru Mizumura, Jun Aketagawa, Toshio Oda, Ken-Ichi Tanamoto
    Biological & pharmaceutical bulletin, 42(12) 2024-2037, Dec 1, 2019  Peer-reviewed
    Assays using lysate reagents prepared from horseshoe crab hemocyte extract (limulus amoebocyte lysate, LAL) are commonly and widely used to detect and measure endotoxin in parenteral drugs and medical devices. However, lysate reagents suffer from lot-to-lot variations leading to possible fluctuations in testing. Also, this continued usage of lysate reagents leads to the possible decline of the horseshoe crab population. Recently, a new recombinant chromogenic reagent, PyroSmart, consisting of three recombinant factors was introduced to the market. There are now three recombinant products; two with recombinant factor C reagents and PyroSmart with the complete recombinant LAL system. We evaluated the applicability of the reagent to the harmonized bacterial endotoxins test in the United States, European and Japanese pharmacopeias. The recombinant product showed equivalent potency of thirteen endotoxins from different bacterial strains to conventional chromogenic lysate reagents as long as their assay modes are identical. All analytical characteristics or assay parameters of the reagent satisfied the acceptance criteria which are set for the use for the bacterial endotoxins test filed in the pharmacopeias. All of 109 parenteral drugs tested can be measured with PyroSmart within respective maximum allowable dilutions. The lot-to-lot variation in recovery of endotoxin added in the parenteral drugs for PyroSmart was equal to or less than those of six limulus lysate reagents. In conclusion, the present study suggests that the recombinant reagent, PyroSmart, provide a good alternative to the LAL reagents with better lot-to-lot variation.

Misc.

 60
  • M KIMURA, KIMURA, I, M MUROI, K TANAKA, H NOJIMA, T UWANO
    JAPANESE JOURNAL OF PHARMACOLOGY, 60(1) 19-24, Sep, 1992  Peer-reviewed
    The essential moieties in p-phenylene-polymethylene bis-ammonium (PMBA) derivatives, C6H4[X(CH2)(n)N+R3]2, on the potentiating effects by beta-eudesmol, a main component of Atractylodes lancea, of their neuromuscular blockades were investigated in isolated phrenic nerve-diaphragm muscle preparations of normal and alloxan-diabetic mice. PMBA derivatives were separated into the following three groups based on the patterns of the potentiating effects: group I: PMBA-23 (n = 6, R = Me) and PMBA-24 (n = 6, R = Et); group 11: PMBA-1 (n = 4, R = Me), PMBA-21 (n = 4, R = Et) and PMBA-2 (X = O, n = 3, R = Me); and group III: PMBA-31 (X = S, n = 3, R = Me), PMBA-3 (X = CO, n = 3, R = Me) and PMBA-4 (X = CHOH, n = 3, R = Me). The pretreatment with 80 muM beta-eudesmol for 60 min did not affect group I-induced neuromuscular blocking action, and it potentiated group II- and group III-induced ones. The potentiating effect of beta-eudesmol on group III was greater in diabetic muscles than in normal ones and that on group II was to the same extent in both muscles. These results suggest that the four-methylene length of the side chains in normal muscles and the hydrophilic moieties adjacent to a phenylene ring in diabetic muscles are related to the potentiating effect by beta-eudesmol on PMBA derivatives.
  • H NOJIMA, M MUROI, KIMURA, I, M KIMURA
    BRITISH JOURNAL OF PHARMACOLOGY, 105(1) 23-26, Jan, 1992  Peer-reviewed
    1 The effect of extracellular calcium on single acetylcholine (ACh)-activated channel activities when desensitizing concentrations of succinylcholine (SuCh) were applied to the surrounding endplate membrane was investigated by the cell-attached patch-clamp technique at endplates of single skeletal muscle (flexor digitorum brevis) fibres of adult mice. 2 Bath-applied SuCh (0.1-3-mu-M, in 2.5 mM Ca2+) increased in a concentration-dependent manner the mean open time of ACh-activated channel currents recorded at membrane potentials which cancelled the SuCh-induced depolarizations. 3 In the presence of 0.5 and 2.5 mM external Ca2+, SuCh (3-mu-M) applied outside the patch pipette prolonged the mean open time of ACh-activated channel currents in a time-dependent manner (by 45% and 52%, respectively), and simultaneously significantly decreased the single channel conductance (by 14% and 10%, respectively). These SuCh-induced effects did not occur in a nominally Ca2+-free extracellular medium. 4 Under the same conditions, SuCh (3-mu-M) augmented the time-dependent decline in the opening frequency of ACh-activated channel currents obtained in nominally Ca2+-free medium. 5 These results suggest that external calcium ions act to modulate nicotinic ACh receptor channel activity, and accelerate desensitization of the receptor.
  • M KIMURA, H NOJIMA, M MUROI, KIMURA, I
    NEUROPHARMACOLOGY, 30(8) 835-841, Aug, 1991  Peer-reviewed
    Beta-Eudesmol, an uncharged alcohol contained in Atractylodes lancea, blocks the neuromuscular junction. Atractylodes lancea is prescribed in a traditional Chinese medicine and plays a main role for "alleviation of pain in skeletal muscle". By using the cell-attached patch-clamp or conventional intracellular technique, the site of action of beta-eudesmol on the nicotinic acetylcholine (ACh) receptor (nAChR) channel in skeletal muscle of the adult mouse, was investigated and compared with that of different types of blockers of the nicotinic ACh receptor channel (bupivacaine, chlorpromazine and phencyclidine). Beta-Eudesmol (200-mu-M) depressed completely the nerve-evoked twitch tension and reduced the amplitude and quantal size of endplate potentials but did not alter either the quantal content, resting membrane potential or action potential. Beta-Eudesmol (100-200-mu-M) decreased the amplitude of ACh potentials and accelerated the slow decay of depolarization, induced by the continuous application of ACh. Beta-Eudesmol (40-mu-M) and phencyclidine (10-mu-M) decreased both the open time and opening frequency, without affecting the single channel conductance. Bupivacaine (10-mu-M) decreased only the open time. Chlorpromazine (10-mu-M) decreased only the opening frequency. These results indicate that the blocking effect of beta-eudesmol on nerve-evoked contraction, was due to blockade of nicotinic ACh receptor channels at the neuromuscular junction. Like phencyclidine, beta-eudesmol blocked the nicotinic ACh receptor channel in both the open and closed conformations, and accelerated the desensitization of the nicotinic ACh receptor.
  • M MUROI, KIMURA, I, M KIMURA
    NEUROPHARMACOLOGY, 29(6) 567-572, Jun, 1990  Peer-reviewed
  • M MUROI, K TANAKA, KIMURA, I, M KIMURA
    JAPANESE JOURNAL OF PHARMACOLOGY, 50(1) 69-71, May, 1989  Peer-reviewed
  • M KIMURA, M MUROI, KIMURA, I, S SAKAI, KITAGAWA, I
    JAPANESE JOURNAL OF PHARMACOLOGY, 48(2) 290-293, Oct, 1988  Peer-reviewed
  • Masayasu Kimura, Ikuko Kimura, Masashi Muroi, Masao Yoshizaki, Hiroshi Hikino
    Phytotherapy Research, 1(3) 107-113, 1987  Peer-reviewed
    The pharmacological interaction between constituents of Keishi‐ka‐zyutubu‐tō (composed of 7 crude drugs, namely peony, liquorice, jujube, cassia, ginger, Atractylodes lancea, and aconite), a medicine of Japanese‐Sino origin, was investigated in in situ sciatic nerve‐gastrocnemius muscle preparations using genetically dlabetic KK‐CAy mice. When administered intra‐arterially, the drug caused a degree of inhibition of the diabetic neuromuscular junction 280 times greater than normal. The two constituents, peony‐liquorice, were only 2.6 times more potent in diabetic muscles. When further combined with peony‐liquorice, the potency ratio was increased 4.9 times for cassia, 5.9 times for ginger and 8.7 times for Atractylodes lancea. In combination with the representative compounds contained in the above crude drugs except for jujube, the potency ratio of paeoniflorin (PF) and glycyrrhizin (GLR) was increased 6.6 times for cinnamaldehyde, 6.1 times for [8]‐gingerol and 14 times for β‐eudesmol in diabetic muscles. Aconite potentiated the blocking effects of peony‐liquorice to the same extent in diabetic muscles as in normal muscles. This tendency was also confirmed when mesaconitine was combined with PF‐GLR. The single effect of β‐eudesmol or [8]‐gingerol was 5.2 times or 3.7 times more potent, respectively, on diabetic muscles than on normal muscles. Cinnamaldehyde or mesaconitine demonstrated the same degree of sensitivity in both diabetic and normal muscles. These results indicated that the preferentially more potent neuromuscular blocking effects of Keishi‐ka‐zyutubu‐tō in diabetic muscles were mainly attributable to β‐eudesmol, a major component of Atractylodes lancea. Copyright © 1987 John Wiley &amp Sons, Ltd.
  • M KIMURA, KIMURA, I, M MUROI, T NAKAMURA, S SHIBATA
    JAPANESE JOURNAL OF PHARMACOLOGY, 41(2) 263-265, Jun, 1986  Peer-reviewed
  • M KIMURA, KIMURA, I, H NOJIMA, M MUROI
    JAPANESE JOURNAL OF PHARMACOLOGY, 40(2) 251-256, Feb, 1986  Peer-reviewed
  • M KIMURA, KIMURA, I, K TAKAHASHI, M MUROI, M YOSHIZAKI, M KANAOKA, KITAGAWA, I
    JAPANESE JOURNAL OF PHARMACOLOGY, 36(3) 275-282, 1984  Peer-reviewed

Books and Other Publications

 19

Presentations

 135

Works

 2

Research Projects

 8

Industrial Property Rights

 1

資格・免許

 1
  • Subject
    薬剤師
    Date
    1984/05

実務経験を有する者についての特記事項(職務上の実績)

 2
  • Subject
    大学との共同研究
    Date(From)
    2001
    Date(To)
    2009
    Summary
    北里大学、東京大学(細菌内毒素によるマクロファージ活性化機構に関する研究
  • Subject
    企業との共同研究
    Date(From)
    2009
    Date(To)
    2009
    Summary
    生化学バイオビジネス(株):新規エンドトキシン活性評価系の確立および局方収載試験法との比較