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Commensal microbiota contributes to chronic endocarditis in TAX1BP1 deficient mice.

ABSTRACT: Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-?B by editing the ubiquitylation of target molecules by its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mice develop age-dependent inflammatory constitutions in multiple organs manifested as valvulitis or dermatitis and succumb to premature death. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed 588 gene transcription alterations from the wild type. SAA3 (serum amyloid A3), CHI3L1, HP, IL1B and SPP1/OPN were induced 1,180-, 361-, 187-, 122- and 101-fold respectively. WIF1 (Wnt inhibitory factor 1) exhibited 11-fold reduction. Intense Saa3 staining and significant I-?B? reduction were reconfirmed and massive infiltration of inflammatory lymphocytes and edema formation were seen in the area. Antibiotics-induced 'germ free' status or the additional MyD88 deficiency significantly ameliorated TAX1BP1-KO mice's inflammatory lesions. These pathological conditions, as we named 'pseudo-infective endocarditis' were boosted by the commensal microbiota who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation caused by the ubiquitin remodeling immune regulators and fatal cardiac dysfunction.

SUBMITTER: Nakano S

PROVIDER: S-EPMC3785488 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Commensal microbiota contributes to chronic endocarditis in TAX1BP1 deficient mice.

Nakano Satoko S Ikebe Emi E Tsukamoto Yoshiyuki Y Wang Yan Y Matsumoto Takashi T Mitsui Takahiro T Yahiro Takaaki T Inoue Kunimitsu K Kawazato Hiroaki H Yasuda Aiko A Ito Kanako K Yokoyama Shigeo S Takahashi Naohiko N Hori Mitsuo M Shimada Tatsuo T Moriyama Masatsugu M Kubota Toshiaki T Ono Katsushige K Fujibuchi Wataru W Jeang Kuan-Teh KT Iha Hidekatsu H Nishizono Akira A

PloS one 20130927 9

Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules by its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mice develop age-dependent inflammatory constitutions in multiple organs manifested as valvulitis or dermatitis and succumb to premature death. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed 588 gene transcription alterations f ...[more]

PMID: 24086273

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Project description:Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules with its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mouse develops age-dependent inflammatory constitution in multiple organs including heart, liver, skin and succumb to premature heart failure. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed that the 588 transcription alterations. SAA3 (serum amyloid A3), at 1,180-fold induction (FI), CHI3L1(361-FI), HP(187-FI), IL1B(122-FI) and SPP1/OPN(101-FI) and WIF1 (Wnt inhibitory factor 1) at 11-fold decrease implied extensive inflammation and tissue degeneration at this microenvironment. Intense Saa3 staining and significant reduction of I-κBα at the same area, massive infiltration of inflammatory lymphocytes and edema formation at the peripheral areas of sinoatrial and atrioventricular node were also observed and electrocardiogram indicated atrioventricular conduction defect (elongated PQ-interval) in TAX1BP1-KO mice. Since antibiotics-induced ‘germ free’ status for three months significantly ameliorated these chronic autoimmune and altered cardiac excitation properties, we conclude that these chronic pathological conditions, as we named ‘pseudo-infective endocarditis’ were boosted by the commensal microbiota those who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation and cardiac dysfunction. We employed laser capture microdissection (LCM) and gene expression microarray technique to obtain the specific gene expression information of pathologic organ. Total RNAs of mitral valves from three independent tissues of 8- or 16-week age (-wk) male mice of either WT or TAX1BP1-KO mice were prepared by LCM followed by total RNA extraction kit. Then the global mRNA expression profiles were analyzed by Agilent gene expression microarray.

Dataset Information

Commensal microbiota contributes to chronic endocarditis in TAX1BP1 deficient mice.

Publications

Commensal microbiota contributes to chronic endocarditis in TAX1BP1 deficient mice.

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