2002 Fiscal Year Annual Research Report

Toll-like receptor発現と遺伝子多型によるH.P関連疾患の解析

Research Project

Project/Area Number	13670520
Research Institution	Shimane Medical University
Principal Investigator	石原俊治島根医科大学, 医学部, 講師 (80263531)
Keywords	Toll like receptor / MD-2 / H.pylori / innate immunity
Research Abstract	本研究は、内視鏡検査時に採取されたヒト胃粘膜生検組織および株化されたヒト胃粘膜培養細胞を用いて検討を行った.免疫組織学的手法、RT-PCR法を用いた検討では、ヒト胃粘膜では上皮細胞および浸潤マクローファージにTLR-4とその共役分子であるMD-2が発現していること、さらにTLR-4とMD-2はH.pylori感染によって有意に発現が増強されることを見い出した.また、TLR-4とMD-2のcDNA全長をクローニング後に遺伝子発現ベクターを作製し、HEK293T細胞、AGS細胞を用いてこれらの遺伝子が一過性あるいは恒常的に発現する系を確立した.作製した遺伝子導入細胞をH.pylori由来のLPSで刺激すると、MD-2の発現依存的にNFκ-B、Interleukin-8プロモーターの活性が増加することがルシフェラーゼアッセイによって明かとなった.また、MD-2を恒常発現する胃粘膜上皮細胞では、細胞質内のTLR-4蛋白が有意に細胞表面へ表出されるこもともフローサイトメトリーにて解明した.これらの結果から、H.pylori感染の病態においてはTLR-4/MD-2を介した自然免疫機構が関与し、特にMD-2の発現がTLR-4蛋白の機能を制御しており、胃粘膜におけるH.pyloriに対する宿主の自然免疫応答を規定している可能性が示唆された.現在も本研究は継続中であるが、H.pylori感染者における疾患多様性の病態にアプローチするため、あるいは炎症性腸疾患の病態にもTLR-4/MD-2を介した自然免疫機構が密接に関与することが考えらるため、研究の着眼点をMD-2の発現制御機構においている.既に、MD-2プロモーターのより機能的な部位である約1kbの領域をクローニングし、H.pyloriや種々のサイトカインによるMD-2の発現制御機構について検討中である.

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Okuyama T, et al.: "A novel doudenal elevated lesion mimicking intraluminal doudenal"Gastrointestinal Endoscopy. 55. 750-752 (2002)
[Publications] Kazumori H, et al.: "Localization of Reg receptor in rat fundic mucosa"J. Lab. Clin. Med. 139. 101-108 (2002)
[Publications] Takashima T, et al.: "Cardiovascular risk factors in subjects with Helicobacter pylori"Helicobacter. 7. 86-90 (2002)
[Publications] Kawashima K, et al.: "Locolization of calcitonin gene-related peptide receptors in rat"Peptides. 23. 955-966 (2002)
[Publications] Kaji T, et al.: "Adherence of Helicobacter pylori to gastric epithelial"J. Lab. Clin. Med. 139. 244-250 (2002)
[Publications] Kazumori H, et al.: "Time course changes of ECL cell markers in acetic acid-induced"Alimentary pharmacology and Therapeutics. 16. 10-19 (2002)
[Publications] Sato H, et al.: "Primary hyperparathyroidism with duodenal ulcer and"Internal Medicine. 41. 377-380 (2002)
[Publications] Rumi Mak, et al.: "Growth inhibition of esophageal squamous carcinoma cells"J. Lab. Clin med. 140. 17-26 (2002)
[Publications] Adachi K, et al.: "Comparative evaluation of urine-based and other minimally invasive"J. Gastroenterology. 37. 703-708 (2002)
[Publications] Sato H, et al.: "Successful endoscopic injection sclerotherapy for duodenal"J. Gastroenterology. 37. 143-144 (2002)
[Publications] Kawamura A, et al.: "Helicobacter pylori-independent effect of hyperglycemia on gastric"Am. J. Gastroenterol. 97. 2479-2480 (2002)
[Publications] Okuyama T, et al.: "Activation of prostaglandin E2 receptor"J. Lab. Clin. Med. 140. 92-102 (2002)
[Publications] Okuyama T, et al.: "Angiolipoma of the colon diagnosed after endoscopic"Gastrointest Endosc. 55. 748-750 (2002)
[Publications] Yoshino N, et al.: "Helicobacter pylori infection does not affect the serum"Am J Gastroenterol. 97. 2979-2928 (2002)
[Publications] Ortaga-Cava CE, et al.: "Hepatocyte growth factor expression in dextran sodium"Dig. Dis. Sci. 47. 2275-2285 (2002)
[Publications] Kadowaki Y, et al.: "Reg protein is overexpressed in gastric cancer cells"FEBS Lett.. 530. 59-64 (2002)
[Publications] Sato H, et al.: "Lafutidine pretreatment causes increase in serum"J. Lab. Clin. Med. 141. 102-105 (2003)
[Publications] Fujishiro H, et al.: "Analysis of urgent colonoscopy for acute lower intestinal"Digestive Endoscopy. 15. 117-120 (2003)

2002 Fiscal Year Annual Research Report

Toll-like receptor発現と遺伝子多型によるH.P関連疾患の解析

Principal Investigator

石原 俊治 島根医科大学, 医学部, 講師 (80263531)

Research Products

[Publications] Okuyama T, et al.: "A novel doudenal elevated lesion mimicking intraluminal doudenal"Gastrointestinal Endoscopy. 55. 750-752 (2002)

[Publications] Kazumori H, et al.: "Localization of Reg receptor in rat fundic mucosa"J. Lab. Clin. Med. 139. 101-108 (2002)

[Publications] Takashima T, et al.: "Cardiovascular risk factors in subjects with Helicobacter pylori"Helicobacter. 7. 86-90 (2002)

[Publications] Kawashima K, et al.: "Locolization of calcitonin gene-related peptide receptors in rat"Peptides. 23. 955-966 (2002)

[Publications] Kaji T, et al.: "Adherence of Helicobacter pylori to gastric epithelial"J. Lab. Clin. Med. 139. 244-250 (2002)

[Publications] Kazumori H, et al.: "Time course changes of ECL cell markers in acetic acid-induced"Alimentary pharmacology and Therapeutics. 16. 10-19 (2002)

[Publications] Sato H, et al.: "Primary hyperparathyroidism with duodenal ulcer and"Internal Medicine. 41. 377-380 (2002)

[Publications] Rumi Mak, et al.: "Growth inhibition of esophageal squamous carcinoma cells"J. Lab. Clin med. 140. 17-26 (2002)

[Publications] Adachi K, et al.: "Comparative evaluation of urine-based and other minimally invasive"J. Gastroenterology. 37. 703-708 (2002)

[Publications] Sato H, et al.: "Successful endoscopic injection sclerotherapy for duodenal"J. Gastroenterology. 37. 143-144 (2002)

[Publications] Kawamura A, et al.: "Helicobacter pylori-independent effect of hyperglycemia on gastric"Am. J. Gastroenterol. 97. 2479-2480 (2002)

[Publications] Okuyama T, et al.: "Activation of prostaglandin E2 receptor"J. Lab. Clin. Med. 140. 92-102 (2002)

[Publications] Okuyama T, et al.: "Angiolipoma of the colon diagnosed after endoscopic"Gastrointest Endosc. 55. 748-750 (2002)

[Publications] Yoshino N, et al.: "Helicobacter pylori infection does not affect the serum"Am J Gastroenterol. 97. 2979-2928 (2002)

[Publications] Ortaga-Cava CE, et al.: "Hepatocyte growth factor expression in dextran sodium"Dig. Dis. Sci. 47. 2275-2285 (2002)

[Publications] Kadowaki Y, et al.: "Reg protein is overexpressed in gastric cancer cells"FEBS Lett.. 530. 59-64 (2002)

[Publications] Sato H, et al.: "Lafutidine pretreatment causes increase in serum"J. Lab. Clin. Med. 141. 102-105 (2003)

[Publications] Fujishiro H, et al.: "Analysis of urgent colonoscopy for acute lower intestinal"Digestive Endoscopy. 15. 117-120 (2003)

石原俊治島根医科大学, 医学部, 講師 (80263531)