Phosphodiesterase inhibitors inhibit Lactobacillus casei cell-wall-induced inflammations

• Project/Area Number: 24591572
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kanazawa University
• Principal Investigator: SAITO Takekatsu 金沢大学, 大学病院, 助教 (30525035)
• Co-Investigator(Kenkyū-buntansha): OHTA Kunio 金沢大学, 医学系, 准教授 (00303280) ; SUGIMOTO Naotoshi 金沢大学, 医学系, 准教授 (80272954)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 小児科 / 循環器 / 病態 / 炎症 / 臨床

Outline of Final Research Achievements

Kawasaki disease patients show the symptoms of a fever and vasculitis, and sometimes severe coronary artery aneurysm. This coronary artery aneurysm might result in lowering the QOL of children. Lactobacillus Lactobacillus casei cell wall fragments (LCWE) make similar Kawasaki disease in animals. Previously we showed that cAMP down-regulates the inflammatory response. In this study, we revealed that cAMP inhibits the LCWE-induced NF-kappaB and MAPK pathways, and cell proliferation. In addition, both the signals of pretein kinase A (PKA) and Epac that are downstream of cAMP are involved.

Research Products

• [Journal Article] Author's reply. (2015)
  • Author(s): Ohta K, Hashida Y, Wada T, Saito T, Kasahara Y, Yachie A.
  • Journal Title: J Cardiol. Volume: S0914-5087(15) Issue: 1 Pages: 00016-17
  • DOI: 10.1016/j.jjcc.2015.01.005
  • Peer Reviewed
• [Journal Article] Early diagnosis of Danon disease: Flow cytometric detection of lysosome-associated membrane protein-2-negative leukocytes. (2014)
  • Author(s): Hashida Y, Wada T, Saito T, Ohta K, Kasahara Y, Yachie A.
  • Journal Title: J Cardiol. Volume: S0914-5087(14) Issue: 2 Pages: 00287-291
  • DOI: 10.1016/j.jjcc.2014.09.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Rotavirus gastroenteritis-associated urinary ammonium acid urate crystals (2014)
  • Author(s): Yokoyama T, Sugimoto N, Kato E, Ohta K, Ishikawa S, Ueno K, Shimizu M, Yachie, A
  • Journal Title: Pediatrics International Volume: 57 Issue: 1 Pages: 158-160
  • DOI: 10.1111/ped.12405
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Shiga toxin-2 enhances heat-shock-induced cell death in cultured and primary glial cells. (2014)
  • Author(s): Sugimoto N, Toma T, Shimizu M, Kuroda M, Wada T, Yachie A.
  • Journal Title: Cell Biol Toxicol Volume: 30 Issue: 5 Pages: 289-299
  • DOI: 10.1007/s10565-014-9286-1
  • Peer Reviewed / Open Access
• [Journal Article] Theobromine, the primary methylxanthine found in Theobroma cacao, prevents malignant glioblastoma proliferation by negatively regulating phosphodiesterase-4, extracellular signal-regulated kinase, Akt/mammalian target of rapamycin kinase, and nuclear factor-kappa B (2014)
  • Author(s): Sugimoto N, Miwa S, Hitomi Y, Nakamura H, Tsuchiya H, Yachie A
  • Journal Title: Nutr Cancer Volume: 66(3) Issue: 3 Pages: 419-23
  • DOI: 10.1080/01635581.2013.877497
  • Peer Reviewed
• [Journal Article] Circumstances and Outcomes of Out-Of-Hospital Cardiac Arrest in Elementary and Middle School Students in the Era of Public-Access Defibrillation (2014)
  • Author(s): Mitani Y, Ohta K, Ichida F, Nii M, Arakaki Y, Ushinohama H, Takahashi T, Ohashi H, Yodoya N, Fujii E, Ishikura K, Tateno S, Sato S, Suzuki T, Higaki T, Iwamoto M, Yoshinaga M, Nagashima M, Sumitomo N.
  • Journal Title: Circulation Journal Volume: 78 Issue: 3 Pages: 701-707
  • DOI: 10.1253/circj.CJ-13-1162
  • NAID: 130003391007
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Public access defibrillation improved the outcome after out-of-hospital cardiac arrest in school-age children: a nationwide, population-based, Utstein registry study in Japan (2013)
  • Author(s): Mitani Y, Ohta K, Yodoya N, Otsuki S, Ohashi H, Sawada H, Nagashima M, Sumitomo N, Komada Y.
  • Journal Title: Europace Volume: 15 Issue: 9 Pages: 1259-66
  • DOI: 10.1093/europace/eut053
  • Peer Reviewed
• [Journal Article] Lactobacillus casei cell wall extract directly stimulates the expression of COX2 independent of Toll-like receptor 2 in rat glial cells (2013)
  • Author(s): Sugimoto N, Ohta K, Saito T, Nakayama Y, Nakamura T, Maeda A, Yachie A.
  • Journal Title: J Microbiol Immunol Infect. Volume: 46 Issue: 5 Pages: 389-92
  • DOI: 10.1016/j.jmii.2012.03.004
  • NAID: 120004161555
  • Peer Reviewed
• [Journal Article] Targeted activation of PKA and Epac promotes glioblastoma regression in vitro (2013)
  • Author(s): Sugimoto N, Miwa S, Tsuchiya H, Hitomi Y, Nakamura H, Yachie A, Koizumi S
  • Journal Title: Mol Clin Oncol Volume: 1(2) Issue: 2 Pages: 281-285
  • DOI: 10.3892/mco.2013.65
  • Peer Reviewed
• [Journal Article] Upregulation of aquaporin expression in the salivary glands of heat-acclimated rats (2013)
  • Author(s): Sugimoto N, Matsuzaki K, Ishibashi H, Tanaka M, Sawaki T, Fujita Y, Kawanami T, Masaki Y, Okazaki T, Sekine J, Koizumi S, Yachie A, Umehara H and Shido O
  • Journal Title: Scientific Reports Volume: 3 Issue: 1 Pages: 1763-1763
  • DOI: 10.1038/srep01763
  • Peer Reviewed
• [Journal Article] Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy (2013)
  • Author(s): Miwa S, Yano S, Tome Y, Sugimoto N, Hiroshima Y, Uehara F, Mii S, Kimura H, Hayashi K, Efimova EV, Fujiwara T, Tsuchiya H, Hoffman RM
  • Journal Title: J Cell Biochem Volume: 114(11) Issue: 11 Pages: 2454-60
  • DOI: 10.1002/jcb.24593
  • Peer Reviewed
• [Journal Article] 心房中隔欠損症における心電図所見の検討：下方誘導のnotchは有用か (2013)
  • Author(s): 中村太地、斉藤剛克、中山祐子、橋田暢子、太田邦雄
  • Journal Title: 日本小児循環器学会誌 Volume: 29 Pages: 322-327
  • Peer Reviewed
• [Journal Article] Anomalous origin with myocardial bridging in coronary artery: stealth images in computed tomography. (2012)
  • Author(s): Yamamoto R, Kawashiri MA, Tada H, Tsubokawa T, Uchiyama K, Konno T, Hayashi K, Saito T, Ohta K, Yachie A, Yamagishi M.
  • Journal Title: J Am Coll Cardiol. Volume: 60 Issue: 23 Pages: 2419-2419
  • DOI: 10.1016/j.jacc.2012.03.085
  • NAID: 120005253226
  • Peer Reviewed
• [Journal Article] Natural history of medium-sized atrial septal defect in pediatric cases. (2012)
  • Author(s): Saito T, Ohta K, Nakayama Y, Hashida Y, Maeda A, Maruhashi K, Yachie A.
  • Journal Title: J Cardiol. Volume: 60 Issue: 3 Pages: 248-251
  • DOI: 10.1016/j.jjcc.2012.05.005
  • Peer Reviewed
• [Journal Article] Phosphodiesterase Inhibitors Suppress Lactobacillus casei Cell-Wall-Induced NF-κB and MAPK Activations and Cell Proliferation through Protein Kinase A-or Exchange Protein Activated by cAMP-Dependent Signal Pathway (2012)
  • Author(s): Saito T, Sugimoto N, Ohta K, Shimizu T, Ohtani K, Nakayama Y, Nakamura T, Hitomi Y, Nakamura H, Koizumi S, Yachie A
  • Journal Title: The Scientific World Journal Volume: 2012 Pages: 748572-748572
  • DOI: 10.1100/2012/748572
  • Peer Reviewed
• [Journal Article] 救命 自動体外式除細動器(AED)、同期下カルディオバージョン (2012)
  • Author(s): 斉藤 剛克
  • Journal Title: 小児科診療 Volume: 75 Pages: 20-25
• [Presentation] 志賀毒素のグリア細胞への作用 (2014)
  • Author(s): 杉本直俊、東馬智子、清水正樹、黒田文人、和田泰三、谷内江昭宏
  • Organizer: 第８回スフィンゴテラピー研究会
  • Place of Presentation: 山中温泉河鹿荘ロイヤルホテル（石川県加賀市）
  • Year and Date: 2014-07-12 – 2014-07-13
• [Presentation] 「学校検診管理症例の脱落を防ぐ」 (2014)
  • Author(s): 斉藤剛克、太田邦雄
  • Organizer: 第50回日本小児循環器学会
  • Place of Presentation: 岡山コンベンションセンター（岡山市）
  • Year and Date: 2014-07-03 – 2014-07-05
• [Presentation] 小学校高学年に対する心肺蘇生法教育の可能性 (2012)
  • Author(s): 太田 邦雄, 中山 祐子, 斉藤 剛克, 谷内江 昭宏
  • Organizer: 第26回日本小児救急医学会
  • Place of Presentation: 大田区民ホール アプリコ（東京都）
• [Presentation] 心房中隔欠損における心電図所見の検討 下方誘導のnotchは有用か (2012)
  • Author(s): 中村 太地, 斉藤 剛克ほか
  • Organizer: 第48回日本小児循環器学会
  • Place of Presentation: 国立京都国際会議場（京都府）
• [Presentation] 胎児診断された先天性完全房室ブロック症例の臨床像 (2012)
  • Author(s): 太田 邦雄, 斉藤 剛克ほか
  • Organizer: 第48回日本周産期・新生児医学会
  • Place of Presentation: 大宮ソニックシティ（埼玉県）
• [Presentation] Williams症候群および類縁疾患の治療方針～SVASおよびPPSの自然歴からの考察～ (2012)
  • Author(s): 久保達哉 中村太地 中山裕子 橋田暢子 前田顕子 斉藤剛克 太田邦雄
  • Organizer: 第40回北陸小児循環器研究会
  • Place of Presentation: 金沢大学（石川県）