Decreased Expression of Toll-like Receptor 2 and 4 on Macrophages in Experimental Severe Acute Pancreatitis

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概要

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• In severe acute pancreatitis (SAP), immunologic impairment in the early phase maybe linked to subsequent infectious complications that are main contributor to the highmortality. Toll-like receptors (TLRs) recognize microorganisms as the innate immunesystem, and are involved in host defense mechanism. TLR2 recognizes lipoteichoic acid(LTA) of gram-positive bacteria, and TLR4 recognizes lipopolysaccharide (LPS) ofgram-negative bacilli. This study aimed to investigate the expression of TLRs onmacrophages and their TLRs-mediated cytokine production in rat SAP. SAP wasinduced by retrograde injection of 3% sodium deoxycholate into the biliopancreaticduct in male Wistar rats. Macrophages were isolated from bronchoalveolar lavage fluid6 hours after induction of SAP. The expression of TLR2 and TLR4 was analyzed byreal-time RT-PCR and western blotting. TNF-α release from macrophages wasestimated after 4-hour stimulation of LTA or LPS. Endotoxin/bacterial translocation(E/BT) was also evaluated in this model. The expression of TLR2 (mRNA and protein)and LTA-mediated TNF-α production were significantly decreased in SAP comparedwith control. The expression of TLR4 (mRNA and protein) and LPS-mediated TNF-αproduction was also significantly decreased in SAP compared with control. E/BToccurred 18 hours after induction of SAP. These results suggest that the impairedresponsiveness to LTA and LPS of macrophages is derived from decreased expressionof TLR2 and TLR4, respectively. This suppression of immune response in the earlyphase may be implicated in the mechanism of infectious complications.

• 神戸大学の論文

著者

• Nakamura T

  Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences

• Matsumoto Shin-ichi

  First Department Of Surgery Kobe University School Of Medicine

• Ueda T

  Department Of Surgery Kinki University School Of Medicine

• SAWA Hidehiro

  Department of Surgery, Kobe University Graduate School of Medical Sciences

• TAKEYAMA Yoshifumi

  Department of Surgery, Kinki University School of Medicine

• Matsumura Naoki

  Division of Gastroenterological Surgery, Department of Clinical Molecular Medicine, Kobe University

• Ueda Takeshi

  Division of Gastroenterological Surgery, Department of Clinical Molecular Medicine, Kobe University

• Yasuda Takeo

  Division of Gastroenterological Surgery, Department of Clinical Molecular Medicine, Kobe University

• Shinzeki Makoto

  Division of Gastroenterological Surgery, Department of Clinical Molecular Medicine, Kobe University

• Sawa Hidehiro

  Division of Gastroenterological Surgery, Department of Clinical Molecular Medicine, Kobe University

• Nakajima Takahiro

  Division of Gastroenterological Surgery, Department of Clinical Molecular Medicine, Kobe University

• Kuroda Yoshikazu

  Division of Gastroenterological Surgery, Department of Clinical Molecular Medicine, Kobe University

• SHINKAI MASAYUKI

  First Department of Surgery Kobe University School of Medicine

• Shinzeki Makoto

  Department Of Surgery Kobe University Graduate School Of Medicine

• Shinzeki Makoto

  神戸大学 医学研究科外科学講座

• Matsumura Naoki

  Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences

• Matsumura Naoki

  神戸大学 医学部食道胃腸外科(乳腺外科)

• Kuroda Y

  Department Of Surgery Kobe University Graduate School Of Medicine

• Kuroda Yoshikazu

  神戸大学 医学研究科外科学講座

• Kuroda Y

  Division Of Gastroenterological Surgery Department Of Clinical Molecular Medicine Kobe University Gr

• Kuroda Yoshikazu

  神戸大学 医学系研究科消化器外科学

• Sawa Hidehiro

  Department Of Surgery Kobe University Graduate School Of Medical Sciences

• Sawa Hidehiro

  近畿大学 医学部外科学教室

• Sawa Hidehiro

  Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences

• Takeyama Y

  Department Of Surgery Kinki University School Of Medicine

• Ku Y

  Department Of Hepato-biliary-pancreatic Surgery Kobe University Graduate School Of Medical Sciences

• Ku Yonson

  Department Of Surgery Kobe University Graduate School Of Medical Sciences

• Ku Yonson

  Gastroenterological Surgery Kobe University Graduate School Of Medicine

• Ku Yonson

  Surgery Kobe University Graduate School Of Medicine

• Takeyama Yoshifumi

  Department Of Surgery School Of Medicine Kinki University

• Takeyama Yoshifumi

  Department Of Surgery Kinki University School Of Medicine

• Kuroda Y

  神戸大学 医学研究科外科学講座

• Kuroda Yoshikazu

  Division Of Gastroenterological Surgery Department Of Clinical Molecular Medicine Kobe University Gr

• Nakajima Takahiro

  Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences

• Yamaguchi Tetsu

  1st Dept. Of Intern. Med. Faculty Of Med. Univ. Of Tokyo

• Okumura Katsuhiko

  Department Of Hospital Pharmacy School Of Medicine Kobe University

• Kuroda Yoshikazu

  First Department Of Surgery Faculty Of Medicine Kobe University

• Kuroda Yoshikazu

  Division Of Gastroenterological Surgery Department Of Clinical Molecular Medicine Graduate School Of

• Ku Yonson

  Department Of Gastroenterological Surgery Kobe University Graduate School Of Medicine

• Samizo Masahiro

  First Department Of Surgery Kobe University School Of Medicine

• Okumura Katsuhiko

  Department Of Hospital Pharmacy Kyoto Pharmaceutical University:department Of Hospital Pharmacy Kobe

• Kuroda Yoshikazu

  First Department Of Surgery Kobe University School Of Medicine

• Kuroda Yoshikazu

  Department Of Gastroenterological Surgery Graduate School Of Medical Sciences Kobe University

• Nakamura Takeshi

  Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences

• Nakamura Takatoshi

  Faculty Of Pharmaceutical Sciences Nagoya City University

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