Naozumi Ishimaru

Naozumi Ishimaru
Tokyo Medical and Dental University | TMDU · Department of Oral Pathology

D.D.S., Ph.D.

About

233
Publications
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Publications

Publications (233)
Article
SARS‐CoV‐2‐related proteins, ACE2 and TMPRSS2, are determinants of SARS‐CoV‐2 infection. Although these proteins are expressed in oral‐related tissues, their expression patterns and modulatory mechanisms in the salivary glands remain unknown. We herein showed that full‐length ACE2, which has both a fully functional enzyme catalytic site and high‐af...
Article
Full-text available
The periosteum is the layer of cells that covers nearly the entire surface of every bone. Upon infection, injury or malignancy the bone surface undergoes new growth—the periosteal reaction—but the mechanism and physiological role of this process remain unknown1,2. Here we show that the periosteal reaction protects against cancer invasion into the b...
Article
Full-text available
A method was developed that enables the magnesium chloride (MgCl2)‐activated S‐acetamidomethyl cysteine sulfoxide (Cys(Acm)(O)) to induce the sp²(C−H) sulfenylation of the indole of Trp residues. The reaction operates under mild acidic conditions using acetic acid or an ionic liquid to give the Trp‐sulfenylated products. Other than Trp, all other p...
Article
Aim Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that affects exocrine glands. CXCL10 production from salivary gland ductal cells via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been suggested to be involved in glandular inflammation in pSS. We aimed to investigate JAK1, JAK2, phosp...
Article
Full-text available
Medullary thymic epithelial cells (mTECs) are essential for the establishment of self-tolerance in T cells. Promiscuous gene expression by a subpopulation of mTECs regulated by the nuclear protein Aire contributes to the display of self-genomic products to newly generated T cells. Recent reports have highlighted additional self-antigen-displaying m...
Preprint
A method was developed that enables the magnesium chloride (MgCl2)-activated S-acetamidomethyl cysteine sulfoxide (Cys(Acm)(O)) to induce the sp2(C−H) sulfenylation of the indole ring of Trp residues. The reaction operates under mild acidic conditions using acetic acid or an ionic liquid in a highly Trp-selective manner to give the Trp-sulfenylated...
Preprint
Full-text available
A method was developed that enables the magnesium chloride (MgCl2)-activated S-acetamidomethyl cysteine sulfoxide (Cys(Acm)(O)) to induce the sp2(C−H) sulfenylation of the indole ring of Trp residues. The reaction operates under mild acidic conditions using acetic acid or an ionic liquid in a highly Trp-selective manner to give the Trp-sulfenylated...
Article
Although toxicities of multiwalled carbon nanotube (MWCNT) have been found to be related with activities of macrophages phagocytosing the fibers, the exact relationship between macrophage population and pathogenesis of fibrosis and mesotheliomas induced by MWCNTs is largely unknown. CCL2-CCR2 axis, a major monocyte/macrophage infiltration route, is...
Article
Full-text available
Background Comprehending the molecular mechanisms underlying head and neck squamous cell carcinoma (HNSCC) is vital for the development of effective treatment strategies. Deubiquitinating enzymes (DUBs), which regulate ubiquitin‐dependent pathways, are potential targets for cancer therapy because of their structural advantages. Here we aimed to ide...
Article
Full-text available
Introduction Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease that affects the function of exocrine glands, such as the lacrimal and the salivary glands. Extraglandular lesions and malignant lymphoma also occur during the progressive stage of pSS. We have, herein, focused on the pulmonary lesions of pSS and have aimed clarifying th...
Article
Background The toxicological effects of nanomaterials, such as multi-walled carbon nanotubes (MWCNTs), on the immune system are considerably understood. However, the precise relationship between long-term exposure to MWCNTs and chronic inflammation remains unclear. Methods and Finding In this study, exposure to Taquann-treated MWCNTs (T-CNTs) was...
Article
There were “miracle materials” at the time that were later banned. Most of them were “biopersistent” and had “mild acute toxicity but nasty chronic toxicity”. This toxicity gap had given time to allow for mass use before ban. Most carbon-based nanomaterials are taught to be biopersistent and therefore we investigated their chronic inhalation toxici...
Article
Full-text available
Iroquois homeobox (Irx) genes are TALE-class homeobox genes that are evolutionarily conserved across species and have multiple critical cellular functions in fundamental tissue development processes. Previous studies have shown that Irxs genes are expressed during tooth development. However, the precise roles of genes in teeth remain unclear. Here,...
Article
Full-text available
It recently has been reported that partial‐epithelial–mesenchymal transition (p‐EMT) program is associated with metastasis in head and neck squamous cell carcinoma (HNSCC). We previously have identified POSTN (which encodes periostin) as an invasion‐promoting molecule in HNSCC. Interestingly, POSTN expression is frequently observed in cancer cells...
Article
Full-text available
Objective Innate lymphoid cells (ILCs), including natural killer (NK) cells, ILC1, ILC2, lymphoid tissue-inducer (LTi) cells, and ILC3 cell, play a key role in various immune responses. Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of exocrine glands, such as the lacrimal and salivary glands (SGs)....
Preprint
Full-text available
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that affects exocrine glands, such as salivary and lacrimal glands. The Janus kinase (JAK) /signal transducer and activator of transcription (STAT) pathway are activated in various inflammatory diseases including pSS. This study aimed to investigate the expression of JAK1, JAK2, phosp...
Article
The toxicological effects of nanomaterials, such as carbon nanotubes (CNTs), on the immune system are considerably understood. However, the precise relationship between long-term exposure to CNTs and chronic inflammation remains unclear. In this study, a mouse model of chronic peritonitis was established using intraperitoneal injection of multi-wal...
Article
An analytical platform is required to characterize the short-chain fatty acids (SCFAs) in a mouse model of pathological immune conditions. Therefore, liquid chromatography tandem mass spectrometry combined with 2-picolylamine derivatization and a comprehensive study of SCFAs distribution based on serum, saliva, feces, liver, and brain from a mouse...
Article
Full-text available
Sjögren’s syndrome (SS) is an autoimmune disease especially targeting exocrine glands, such as the salivary and lacrimal glands. A radical therapy for SS based on its etiology has not been established because of the complex pathogenesis of the disease. Several studies have demonstrated a relationship between virus infection and SS pathogenesis. In...
Article
Full-text available
The oral mucosa is one of the first lines of the innate host defense system against microbial invasion. Interferon (IFN) lambda-1 (IFN-λ1), a type III IFN, exhibits type I IFN-like antiviral activity. In contrast to ubiquitously expressed type I IFN receptors, IFN-λ receptor 1 (IFN-λR1), which has higher affinity for type III IFNs than low-affinity...
Article
The α-Fodrin N-terminal portion (AFN) autoantigen is involved in T cell-medicated autoimmune responses in patients with Sjögren’s syndrome. The infiltration of autoreactive T cells and the cleavage products of AFN were found in the salivary gland duct cells, and anti-AFN antibodies were detected in the serum of patients with Sjögren’s syndrome. The...
Article
Lymphocyte activation gene-3 (LAG-3) is a potent inhibitory co-receptor; yet, its functional ligand remains elusive, with distinct potential ligands identified. Here, we investigated the relative contribution of potential ligands, stable peptide-MHC class II complexes (pMHCII) and fibrinogen-like protein 1 (FGL1), to LAG-3 activity in vitro and in...
Article
Full-text available
Galactosialidosis (GS) is a lysosomal cathepsin A (CTSA) deficiency. It associates with a simultaneous decrease of neuraminidase 1 (NEU1) activity and sialylglycan storage. Central nervous system (CNS) symptoms reduce the quality of life of juvenile/adult type GS patients, but there is no effective therapy. Here, we established a novel GS model mou...
Article
Full-text available
Targeted blockade of the checkpoint molecule programmed cell death 1 (PD-1) can activate tumor-specific T cells to destroy tumors, whereas targeted potentiation of PD-1 is expected to suppress autoreactive T cells and alleviate autoimmune diseases. However, the development of methods to potentiate PD-1 remains challenging. Here we succeeded in elic...
Article
Front Cover: The cover image is based on the Research Aritcle von Willebrand factor D and EGF domains regulate ameloblast differentiation and enamel formation by Tsutomu Iwamoto et al., https://doi.org/10.1002/jcp.30667.
Article
Cell- and tissue-specific extracellular matrix (ECM) composition plays an important role in organ development, including teeth, by regulating cell behaviors, such as cell proliferation and differentiation. Here, we demonstrate for the first time that von Willebrand factor D and epidermal growth factor (EGF) domains (Vwde), a previously uncharacteri...
Article
Full-text available
Although 5-fluorouracil (5-FU) is currently used as an anti-cancer chemotherapy, adverse effects such as oral mucositis potentially limit its clinical application. Additionally, the prevention of 5-FU-induced side effects are scarce. Resveratrol is known to decrease oxidative damage and inflammation. In this study, we examined the protective effect...
Article
Full-text available
The ability of cancer cells to undergo partial-epithelial mesenchymal transition (p-EMT), rather than complete EMT, poses a higher metastatic risk. Although Fusobacterium nucleatum mainly inhabits in oral cavity, attention has been focused on the F. nucleatum involvement in colorectal cancer development. Here we examined the p-EMT regulation by F....
Article
Full-text available
Bone loss due to smoking represents a major risk factor for fractures and bone osteoporosis. Signaling through the aryl hydrocarbon receptor (AhR) and its ligands contributes to both bone homeostasis and inflammatory diseases. It remains unclear whether the same AhR signaling axis affects the temporomandibular joint (TMJ). The aim of this study was...
Article
Full-text available
The relationship between autoimmunity and changes in intestinal microbiota is not yet fully understood. In this study, the role of intestinal microbiota in the onset and progression of autoimmune lesions in non-obese diabetic (NOD) mice was evaluated by administering antibiotics to alter their intestinal microenvironment. Flow cytometric analysis o...
Article
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Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells i...
Article
Full-text available
The thymoproteasome expressed specifically in thymic cortical epithelium optimizes the generation of CD8+ T cells; however, how the thymoproteasome contributes to CD8+ T cell development is unclear. Here, we show that the thymoproteasome shapes the TCR repertoire directly in cortical thymocytes before migration to the thymic medulla. We further sho...
Article
Microcystic adnexal carcinoma (MAC) is a rare malignant tumor of skin appendages. MAC grows slowly, but is locally aggressive. The metastatic potential is low, but the recurrence rates are very high owing to insufficient dissection. The most common location of MAC is the skin of the midface of middle-aged adults. There has been no report about MAC...
Article
Full-text available
During mitosis, the chromosomal passenger complex (CPC) ensures the faithful transmission of the genome. The CPC is composed of the enzymatic component Aurora B (AURKB) and the three regulatory and targeting components borealin, INCENP, and survivin (also known as BIRC5). Although the CPC is known to be involved in diverse mitotic events, it is sti...
Article
Full-text available
Hyalinizing clear cell carcinoma (HCCC) is a low-grade epithelial tumor classified as a subtype of salivary gland carcinoma. HCCC occurs most frequently on the palate and base of the tongue. Noteworthy, HCCC arising in the anterior of the tongue is quite rare and it has yet to be fully characterized in the clinical literature. Herein, we present a...
Article
Objective Recent studies have revealed that the ability of cancer cells to undergo intermediate state of EMT, partial EMT (p‐EMT) poses a higher metastatic risk rather than complete EMT. Here we examined the prognostic value of p‐EMT‐related genes in head and neck squamous cell carcinoma (HNSCC) by bioinformatic approaches. Materials and Methods W...
Article
Systemic dry syndrome affects quality of life, and various effective methods are being developed for its treatment. We recently found that rooibos (Aspalathus linearis) extract activates muscarinic M3 receptor and improves dryness in mice and humans. We identified eriodictyol-6-C-β-D-glucoside (E6CG) as the active component affecting the secretory...
Article
Full-text available
Signal transmission from the mechanical forces to the various intracellular activities is a fundamental process during tissue development. Despite their critical role, the mechanism of mechanical forces in the biological process is poorly understood. In this study, we demonstrated that in the response to hydrostatic pressure (HP), the piezo type me...
Article
Full-text available
Common age-related changes in the human eye contribute to the development of dry eye, including decreases in aqueous tear production. Although the infiltration of lymphocytes into the lacrimal glands occurs with age, age-related increases in tear production have also been observed in mice; however, the mechanisms underlying this increase remain unc...
Article
Full-text available
Follicular helper T (Tfh) cells contribute to various immune responses as well as to the pathogenesis of several immune diseases. However, the precise mechanism underlying the onset or development of autoimmunity via Tfh cells remains unclear. Here, the detailed relationship between autoimmune disease and Tfh cells was analyzed using a murine model...
Article
Objectives: Sicca syndrome is characterized by dry mouth and eyes and results in a reduction of the patient's quality of life. Various natural plants, including certain herbs, have long been employed to alleviate such symptoms. Rooibos grown in South Africa is one of the potent herbal plants used for the treating dry mouth. However, the precise me...
Article
Dry mouth is caused by the dysfunction of salivary glands due to various factors. In order to understand the mechanism of dry mouth or develop new therapies for dry mouth, many mice models have been widely used to analyze the function of saliva secretion. In this study, a small amount of saliva was collected using oral pH paper, following stimulati...
Article
Endochondral ossification is important for skeletal development. Recent findings indicate that the p65 (RelA) subunit, a main subunit of the classical nuclear factor-κB (NF-κB) pathway, plays essential roles in chondrocyte differentiation. Although several groups have reported that the alternative NF-κB pathway also regulates bone homeostasis, the...
Article
Full-text available
Macrophages (MΦs) are critical regulators of immune response and serve as a link between innate and acquired immunity. The precise mechanism of involvement of tissue-resident MΦs in the pathogenesis of autoimmune diseases is not clear. Here, using a murine model for Sjögren's syndrome (SS), we investigated the role of tissue-resident MΦs in the ons...
Data
(A) Stromal cells did not express CCL22. CCL22 was detected by immunohistochemical analysis. Bar: 500 and 50 μm. (B–E) Confocal microscopic analysis of CCL22 expression of Keratin+ epithelial cells (B), CD3+ T cells (C), CD19+ B cells (D), and S100+ DCs (E) using the sections of SS patients (Grade 4). Photos are representative of five samples in ea...
Data
Gating strategy and representative gating of immune cells obtained from salivary gland tissues in the SS models. FSC-A/SSC-A, FSC-A/FSC-H, and FSC/CD45.2 panels are shown. After gating single cells and CD45.2+ cells among live cells, 7-AAD−CD3−CD19− cells were gated for obtaining MΦ population.
Data
(A) Intracellular expressions of IFN-γ, IL-4, and IL-17 of activated splenic CD4+ T cells. CD4+ T cells purified from spleen of the control and SS model mice were stimulated with PMA (50 ng/mL) and ionomycin (1 μg/ml) for 6 h with Golgi-stop. Data are representative of three independent experiments. (B) CD4+ T cells purified from the spleen in cont...
Data
(A) mRNA expressions of CXCR3A, CCR3, and CX3CR1 in salivary gland tissues from control and SS model mice at 12 weeks of age were determined by qRT-PCR. Data are presented as mean ± SEM. n = 5. The primer sequences used were as follows: CXCR3A: forward, 5′-TGCTAGATGCCTCGGACTTT-3′, and reverse, 5′- CGCTGACTCAGTAGCACAGC-3′, CCR3: forward, 5′-TTGATCCT...
Article
Full-text available
Background Nanomaterials are widely used in various fields. Although the toxicity of carbon nanotubes (CNTs) in pulmonary tissues has been demonstrated, the toxicological effect of CNTs on the immune system in the lung remains unclear. Methods and finding In this study, exposure to Taquann-treated multi-walled CNTs (T-CNTs) was performed using aer...
Article
Full-text available
CXCL10, a CXC chemokine induced by interferon-gamma [IFN-γ], has been observed in a wide variety of chronic inflammatory disorders and autoimmune conditions. Although CXCL10 is known to be overexpressed in the salivary glands of individuals with primary Sjögren’s syndrome (pSS), it is unclear which cells produce CXCL10 under what types of stimulati...
Article
A variety of infectious diseases are observed in area of oral and maxillofacial surgery. Appropriate diagnosis for them plays a key role in the effective therapy of serious infection. Many infectious diseases in the area of oral and maxillofacial surgery are known, including dental caries, infection in the periodontal tissue, the oral membrane, the...
Article
Background Mechanisms underlying immune cells’ recruitment and activation into the inflammatory lesions of lip salivary glands (LSGs) from primary Sjögren's syndrome (pSS) patients are incompletely understood. Chemokines play pivotal roles in these processes, so we investigated the clinical significance of chemokine receptor CXCR3 and its ligands i...
Article
Full-text available
It is well recognized that the presence of cervical lymph node metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC). In solid epithelial cancer, the first step during the process of metastasis is the invasion of cancer cells into the underlying stroma, breaching the basement membrane (BM)-the natural barrier bet...
Presentation
Full-text available
Abstract Introduction – Chronicity, complexity and indeterminate underlying mechanisms of orofacial neuropathic pain renders its medical management challenging. It has been established that inflammatory cytokines are implicated in the perpetuation and progression of pain. The purpose of this study was to analyze the release and determine the associ...
Presentation
Full-text available
Abstract Introduction – Chronicity, complexity and indeterminate underlying mechanisms of orofacial neuropathic pain renders its medical management challenging. It has been established that inflammatory cytokines are implicated in the perpetuation and progression of pain. The purpose of this study was to analyze the release and determine the associ...
Article
The nuclear receptor aryl hydrocarbon receptor (AhR) plays a crucial role in receptor activator of nuclear factor (NF)-kB ligand (RANKL)-mediated osteoclastogenesis. A considerable amount of evidence reveals that AhR is also a key modulator of skeletal remodeling. However, the mechanism underlying the regulation of AhR expression in osteoclasts and...
Conference Paper
The nuclear receptor aryl hydrocarbon receptor (AhR) plays a crucial role in receptor activator of nuclear factor (NF)-kB ligand (RANKL)-mediated osteoclastogenesis. A considerable amount of evidence reveals that AhR is also a key modulator of skeletal remodeling. However, the mechanism underlying the regulation of AhR expression in osteoclasts and...
Article
Full-text available
Background: Cholangiocarcinoma (CCA) has an abundance of tumor stroma which plays an important role in cancer progression via tumor-promoting signals. This study aims to explore the microRNA (miRNA) profile of CCA-associated fibroblasts (CCFs) and the roles of any identified miRNAs in CCA progression. Methods: miRNA expression profiles of CCFs a...