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Article ; Online: Oxidative stress induces MUC5AC expression through mitochondrial damage‐dependent STING signaling in human bronchial epithelial cells

Yutaka Nishida / Hisako Yagi / Masaya Ota / Atsushi Tanaka / Koichiro Sato / Takaharu Inoue / Satoshi Yamada / Naoya Arakawa / Takashi Ishige / Yasuko Kobayashi / Hirokazu Arakawa / Takumi Takizawa

FASEB BioAdvances, Vol 5, Iss 4, Pp 171-

2023 Volume 181

Abstract: Abstract Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, ... ...

Abstract	Abstract Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, releasing mitochondrial DNA into the cytoplasm and inducing inflammation through the intracytoplasmic DNA sensor STING (stimulator of interferon genes). However, the role of innate immunity in mucin production remains unknown. We aimed to elucidate the role of innate immunity in mucin production in airway epithelial cells under oxidative stress. Human airway epithelial cell line (NCI‐H292) and normal human bronchial epithelial cells were used to confirm MUC5AC expression levels by real‐time PCR when stimulated with hydrogen peroxide (H2O2). MUC5AC transcriptional activity was increased and mitochondrial DNA was released into the cytosol by H2O2. Mitochondrial antioxidants were used to confirm the effects of mitochondrial oxidative stress where antioxidants inhibited the increase in MUC5AC transcriptional activity. Cyclic GMP‐AMP synthase (cGAS) or STING knockout (KO) cells were generated to investigate their involvement. H2O2‐induced MUC5AC expression was suppressed in STING KO cells, but not in cGAS KO cells. The epidermal growth factor receptor was comparably expressed in STING KO and wild‐type cells. Thus, mitochondria and STING play important roles in mucin production in response to oxidative stress in airway epithelial cells.
Keywords	hydrogen peroxide ; mitochondria ; mtDNA ; MUC5AC ; oxidative stress ; STING ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Whipple disease mimicking inflammatory bowel disease

Maiko Tatsuki / Takashi Ishige / Yoshiko Igarashi / Reiko Hatori / Akira Hokama / Junko Hirato / Aleixo Muise / Takumi Takizawa / Hirokazu Arakawa

Intestinal Research, Vol 19, Iss 1, Pp 119-

2021 Volume 125

Abstract: Whipple disease is a systemic chronic infection caused by Tropheryma whipplei. Although chronic diarrhea is a common gastrointestinal symptom, diagnosis is often difficult because there are no specific endoscopic findings, and the pathogen is not ... ...

Abstract	Whipple disease is a systemic chronic infection caused by Tropheryma whipplei. Although chronic diarrhea is a common gastrointestinal symptom, diagnosis is often difficult because there are no specific endoscopic findings, and the pathogen is not detectable by stool culture. We present a female patient with Whipple disease who developed chronic bloody diarrhea and growth retardation at the age of 4 years. Colonoscopy showed a mildly edematous terminal ileum and marked erythema without vascular patterns throughout the sigmoid colon and rectum. Subsequently, a primary diagnosis of ulcerative colitis was made. Histopathological analysis of the terminal ileum showed the presence of foamy macrophages filled with periodic acid-Schiff-positive particles. Polymerase chain reaction using DNA from a terminal ileum biopsy sample amplified a fragment of 16S rRNA from T. whipplei. Antibiotic treatment relieved the patient’s symptoms. There was no evidence of immunodeficiency in the present case. Since Whipple disease worsens after anti-tumor necrosis factor inhibitor therapy, considering this infection in the differential diagnosis may be important in patients with inflammatory bowel disease, especially before initiation of immunotherapy.
Keywords	colitis ; ulcerative ; child ; preschool ; Medicine ; R ; Diseases of the digestive system. Gastroenterology ; RC799-869
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Korean Association for the Study of Intestinal Diseases
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Serological cytokine signature in paediatric patients with inflammatory bowel disease impacts diagnosis

Maiko Tatsuki / Reiko Hatori / Tomoko Nakazawa / Takashi Ishige / Tomoko Hara / Seiichi Kagimoto / Takeshi Tomomasa / Hirokazu Arakawa / Takumi Takizawa

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 11

Abstract: Abstract Endoscopy is a central tool for diagnosing and evaluating paediatric inflammatory bowel diseases (PIBD), but is too invasive to be frequently repeated in young children. Furthermore, it is challenging to distinguish Crohn’s disease (CD) from ... ...

Abstract	Abstract Endoscopy is a central tool for diagnosing and evaluating paediatric inflammatory bowel diseases (PIBD), but is too invasive to be frequently repeated in young children. Furthermore, it is challenging to distinguish Crohn’s disease (CD) from ulcerative colitis (UC) endoscopically. This study aimed to determine biomarkers useful for the diagnosis of PIBD. Cytokines, chemokines, and growth factors were quantified in the sera of 15 patients with CD or UC, at disease onset prior to treatment, and 26 age-matched controls. Correlation of cytokine levels with the paediatric CD activity index (PCDAI) and the paediatric UC activity index (PUCAI) was analysed. Interleukin (IL)-6, IL-13, IL-7, and vascular endothelial growth factor were higher in the CD group than in the UC group. The receiver operating characteristic curve analysis showed that IL-7 was a putative biomarker for distinguishing CD from UC (area under the curve: 0.94). Granulocyte–macrophage colony-stimulating factor was associated with PCDAI, and an IL-1 receptor antagonist, IL-6, and macrophage inflammatory protein-1β were associated with PUCAI. These findings indicate significant differences in cytokine signatures among patients with new-onset PIBD, which may improve accuracy in diagnosing PIBD.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension.

Mitsuru Seki / Nozomi Furukawa / Norimichi Koitabashi / Masaru Obokata / Simon J Conway / Hirokazu Arakawa / Masahiko Kurabayashi

PLoS ONE, Vol 14, Iss 8, p e

2019 Volume 0220795

Abstract: Transforming growth factor beta (TGF-β) has been shown to play a critical role in pathogenesis of pulmonary arterial hypertension (PAH) although the precise role of TGF-β signaling remains uncertain. A recent report has shown that periostin (Pn) is one ... ...

Abstract	Transforming growth factor beta (TGF-β) has been shown to play a critical role in pathogenesis of pulmonary arterial hypertension (PAH) although the precise role of TGF-β signaling remains uncertain. A recent report has shown that periostin (Pn) is one of the most upregulated proteins in human PAH lung compared with healthy lungs. We established type I TGF-β receptor knockout mice specifically with Pn expressing cell (Pn-Cre/Tgfb1fl/fl mice). Increases in PA pressure and pulmonary artery muscularization were induced by hypoxia of 10% oxygen for 4 weeks. Lung Pn expression was markedly induced by 4 week-hypoxia. Pn-Cre/Tgfb1fl/fl mice showed lower right ventricular pressure elevation, inhibition of PA medial thickening. Fluorescent co-immunostaining showed that Smad3 activation in Pn expressing cell is attenuated. These results suggest that TGF-β signaling in Pn expressing cell may have an important role in the pathogenesis of PAH by controlling medial thickening.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Changes in DNA methylation in naïve T helper cells regulate the pathophysiological state in minimal-change nephrotic syndrome

Yasuko Kobayashi / Akira Aizawa / Takumi Takizawa / Katsuhide Igarashi / Izuho Hatada / Hirokazu Arakawa

BMC Research Notes, Vol 10, Iss 1, Pp 1-

2017 Volume 13

Abstract: Abstract Background DNA methylation plays a crucial role in regulating transcription, and changes in DNA methylation affect gene expression and disease development. Minimal change nephrotic syndrome (MCNS) has been reported to involve immunological ... ...

Abstract	Abstract Background DNA methylation plays a crucial role in regulating transcription, and changes in DNA methylation affect gene expression and disease development. Minimal change nephrotic syndrome (MCNS) has been reported to involve immunological disturbances. Since the characteristic features of the disease include recurrent relapse and sex and age preference, the disease pathogenesis may be partly related to epigenetic changes. However, little is known about these changes. Methods We analyzed genome-wide DNA methylation using the microarray-based integrated analysis of methylation by isoschizomers method. This method was used to evaluate methylation in monocytes (patient number; n = 6) and naïve T helper cells (n = 4) from the peripheral blood of MCNS patients both in relapse and following remission and that of healthy controls (n = 5). Results In total, 85 co-occurring genes were identified in naïve T helper cells, while 4 such genes were identified in monocytes, which were common among the 3 following comparisons for changes in DNA methylation using sample pairs: (1) relapse versus remission, (2) relapse versus controls, and (3) remission versus controls. In 82 of 85 co-occurring genes (96.5%) in naïve T helper cells, the level of DNA methylation was altered according to disease activity, but was not related to disease activity in the 4 genes detected in monocytes. Conclusions Therefore, in 82 co-occurring genes in naïve T helper cells, the regulation of DNA methylation was well correlated with the clinical and pathophysiological state. Our genome-wide approach to analyze DNA methylation provides further insight into the pathogenesis of MCNS and indicates potential prediction and diagnostic tool for the disease.
Keywords	Nephrotic syndrome ; Minimal-change ; Children ; DNA methylation ; Microarray-based integrated analysis of methylation by isoschizomers method ; Helper T cell ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
Subject code	610
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes

Chikako Shimokawa / Tamotsu Kato / Tadashi Takeuchi / Noriyasu Ohshima / Takao Furuki / Yoshiaki Ohtsu / Kazutomo Suzue / Takashi Imai / Seiji Obi / Alex Olia / Takashi Izumi / Minoru Sakurai / Hirokazu Arakawa / Hiroshi Ohno / Hajime Hisaeda

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 9

Abstract: Helminth infections are associated with a reduction in inflammatory pathology in rodent models of type 1 diabetes. Here, the authors show patient data and that trehalose (produced by H. polygyrus) can alter the microbiome of mice, inducing regulatory CD8+ ...

Abstract	Helminth infections are associated with a reduction in inflammatory pathology in rodent models of type 1 diabetes. Here, the authors show patient data and that trehalose (produced by H. polygyrus) can alter the microbiome of mice, inducing regulatory CD8+ T cells and reducing susceptibility to autoimmune diabetes.
Keywords	Science ; Q
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 9

Abstract	Helminth infections are associated with a reduction in inflammatory pathology in rodent models of type 1 diabetes. Here, the authors show patient data and that trehalose (produced by H. polygyrus) can alter the microbiome of mice, inducing regulatory CD8+ T cells and reducing susceptibility to autoimmune diabetes.
Keywords	Science ; Q
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Diverse signaling systems activated by the sweet taste receptor in human GLP-1-secreting cells

Ohtsu, Yoshiaki / Hirokazu Arakawa / Itaru Kojima / Masahiro Nagasawa / Shigeki Takeda / Yuko Nakagawa

Molecular and Cellular Endocrinology. 2014 Aug. 25, v. 394

2014

Abstract: Sweet taste receptor regulates GLP-1 secretion in enteroendocrine L-cells. We investigated the signaling system activated by this receptor using Hutu-80 cells. We stimulated them with sucralose, saccharin, acesulfame K and glycyrrhizin. These sweeteners ... ...

Abstract	Sweet taste receptor regulates GLP-1 secretion in enteroendocrine L-cells. We investigated the signaling system activated by this receptor using Hutu-80 cells. We stimulated them with sucralose, saccharin, acesulfame K and glycyrrhizin. These sweeteners stimulated GLP-1 secretion, which was attenuated by lactisole. All these sweeteners elevated cytoplasmic cyclic AMP ([cAMP]c) whereas only sucralose and saccharin induced a monophasic increase in cytoplasmic Ca2+ ([Ca2+]c). Removal of extracellular calcium or sodium and addition of a Gq/11 inhibitor greatly reduced the [Ca2+]c responses to two sweeteners. In contrast, acesulfame K induced rapid and sustained reduction of [Ca2+]c. In addition, glycyrrhizin first reduced [Ca2+]c which was followed by an elevation of [Ca2+]c. Reductions of [Ca2+]c induced by acesulfame K and glycyrrhizin were attenuated by a calmodulin inhibitor or by knockdown of the plasma membrane calcium pump. These results indicate that various sweet molecules act as biased agonists and evoke strikingly different patterns of intracellular signals.
Keywords	acesulfame potassium ; agonists ; Ca2-transporting ATPase ; calcium ; calmodulin ; cyclic AMP ; glucagon-like peptide 1 ; glycyrrhizin ; humans ; plasma membrane ; saccharin ; secretion ; sodium ; sucralose ; taste receptors
Language	English
Dates of publication	2014-0825
Size	p. 70-79.
Publishing place	Elsevier Ireland Ltd
Document type	Article
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2014.07.004
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Reference Values for Japanese Children’s Respiratory Resistance Using the LMS Method

Satomi Hagiwara / Hiroyuki Mochizuki / Reiko Muramatsu / Harumi Koyama / Hisako Yagi / Yutaka Nishida / Tohru Kobayashi / Naoko Sakamoto / Takumi Takizawa / Hirokazu Arakawa

Allergology International, Vol 63, Iss 1, Pp 113-

2014 Volume 119

Abstract: Background:: The forced oscillation technique (FOT) is useful for studying pulmonary function in children, as well as in school children with asthma. However, the standard values for respiratory resistance (Rrs) in Asian school children remain unknown. ... ...

Abstract	Background:: The forced oscillation technique (FOT) is useful for studying pulmonary function in children, as well as in school children with asthma. However, the standard values for respiratory resistance (Rrs) in Asian school children remain unknown. We evaluated the standard Rrs using a type of FOT, impulse oscillometry (IOS), in healthy Japanese children at elementary and junior high schools. Methods:: A total of 795 children (age range: 6-15 years; mean age ± SD: 11.1 ± 2.4 years; 404 boys, 391 girls) at elementary and junior high schools participated in the study. Of the 795 children, we evaluated the Rrs of 537 children aged 6-15 years (mean ± SD: 10.8 ± 2.4 years) using IOS. Results:: Regression analyses with three IOS parameters, Rrs at 5 Hz (R5), Rrs at 20 Hz (R20), and Rrs difference between 5 Hz and 20 Hz (R5-R20), for age, height, weight, and degree of obesity as independent variables demonstrated the strongest correlation between each parameter and children’s height. All parameters decreased with increasing height. Using the lambda-mu-sigma (LMS) method, we created standard curves for the Rrs values based on height. Conclusions:: Our standard curves could be useful for diagnosis and control evaluation of childhood asthma.
Keywords	children ; forced oscillation technique ; LMS method ; reference value ; respiratory resistance ; Medicine ; R ; Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951 ; Immunologic diseases. Allergy ; RC581-607
Subject code	370
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Serum magnesium concentration in children with functional constipation treated with magnesium oxide

Maiko Tatsuki / Reiko Miyazawa / Takeshi Tomomasa / Takashi Ishige / Tomoko Nakazawa / Hirokazu Arakawa

World Journal of Gastroenterology, Vol 17, Iss 6, Pp 779-

2011 Volume 783

Abstract: AIM: To determine whether hypermagnesemia recently reported in adult patients possibly develops in children with functional constipation taking daily magnesium oxide.METHODS: We enrolled 120 patients (57 male and 63 female) aged 1-14 years old (median: 4. ...

Abstract	AIM: To determine whether hypermagnesemia recently reported in adult patients possibly develops in children with functional constipation taking daily magnesium oxide.METHODS: We enrolled 120 patients (57 male and 63 female) aged 1-14 years old (median: 4.7 years) with functional constipation from 13 hospitals and two private clinics. All patients fulfilled the Rome III criteria for functional constipation and were treated with daily oral magnesium oxide for at least 1 mo. The median treatment dose was 600 (500-800) mg/d. Patients were assessed by an interview and laboratory examination to determine possible hypermagnesemia. Serum magnesium concentration was also measured in sex- and age-matched control subjects (n = 38).RESULTS: In the constipation group, serum magnesium concentration [2.4 (2.3-2.5) mg/dL, median and interquartile range] was significantly greater than that of the control group [2.2 (2.0-2.2) mg/dL] (P < 0.001). The highest value was 3.2 mg/dL. Renal magnesium clearance was significantly increased in the constipation group. Serum magnesium concentration in the constipation group decreased significantly with age (P < 0.01). There was no significant correlation between the serum level of magnesium and the duration of treatment with magnesium oxide or the daily dose. None of the patients had side effects associated with hypermagnesemia.CONCLUSION: Serum magnesium concentration increased significantly, but not critically, after daily treatment with magnesium oxide in constipated children with normal renal function.
Keywords	Children ; Constipation ; Hypermagnesemia ; Magnesium oxide ; Renal dysfunction ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	616
Language	English
Publishing date	2011-02-01T00:00:00Z
Publisher	Baishideng Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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