Absence of kynurenine 3-monooxygenase reduces mortality of acute viral myocarditis in mice

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Abstract

Infection of the encephalomyocarditis virus (EMCV) in mice is an established model for viral myocarditis. Previously, we have demonstrated that indoleamine 2,3-dioxygenase (IDO), an L-tryptophan − kynurenine pathway (KP) enzyme, affects acute viral myocarditis. However, the roles of KP metabolites in EMCV infection remain unclear. Kynurenine 3-monooxygenase (KMO) is one of the key regulatory enzymes, which metabolizes kynurenine to 3-hydroxykynurenine in the KP. Therefore, we examined the role of KMO in acute viral infection by comparing between KMO−/− mice and KMO+/+ mice. KMO deficiency resulted in suppressed mortality after EMCV infection. The number of infiltrating cells and F4/80+ cells in KMO−/− mice was suppressed compared with those in KMO+/+ mice. KMO−/− mice showed significantly increased levels of serum KP metabolites, and induction of KMO expression upon EMCV infection was involved in its effect on mortality through EMCV suppression. Furthermore, KMO−/− mice showed significantly suppression of CCL2, CCL3 and CCL4 on day 2 and CXCL1 on day 4 after infection. These results suggest that increased KP metabolites reduced chemokine production, resulting in suppressed mortality upon KMO knockdown in EMCV infection. KP metabolites may thus provide an effective strategy for treating acute viral myocarditis.

Original languageEnglish
Pages (from-to)94-100
Number of pages7
JournalImmunology Letters
Volume181
DOIs
Publication statusPublished - 01-01-2017

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Kynurenine 3-Monooxygenase
Myocarditis
Kynurenine
Encephalomyocarditis virus
Mortality
Virus Diseases
Indoleamine-Pyrrole 2,3,-Dioxygenase
Enzymes
Infection
Chemokines
Tryptophan

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

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title = "Absence of kynurenine 3-monooxygenase reduces mortality of acute viral myocarditis in mice",
abstract = "Infection of the encephalomyocarditis virus (EMCV) in mice is an established model for viral myocarditis. Previously, we have demonstrated that indoleamine 2,3-dioxygenase (IDO), an L-tryptophan − kynurenine pathway (KP) enzyme, affects acute viral myocarditis. However, the roles of KP metabolites in EMCV infection remain unclear. Kynurenine 3-monooxygenase (KMO) is one of the key regulatory enzymes, which metabolizes kynurenine to 3-hydroxykynurenine in the KP. Therefore, we examined the role of KMO in acute viral infection by comparing between KMO−/− mice and KMO+/+ mice. KMO deficiency resulted in suppressed mortality after EMCV infection. The number of infiltrating cells and F4/80+ cells in KMO−/− mice was suppressed compared with those in KMO+/+ mice. KMO−/− mice showed significantly increased levels of serum KP metabolites, and induction of KMO expression upon EMCV infection was involved in its effect on mortality through EMCV suppression. Furthermore, KMO−/− mice showed significantly suppression of CCL2, CCL3 and CCL4 on day 2 and CXCL1 on day 4 after infection. These results suggest that increased KP metabolites reduced chemokine production, resulting in suppressed mortality upon KMO knockdown in EMCV infection. KP metabolites may thus provide an effective strategy for treating acute viral myocarditis.",
author = "Hisako Kubo and Masato Hoshi and Akihiro Mouri and Chieko Tashita and Yasuko Yamamoto and Toshitaka Nabeshima and Kuniaki Saito",
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T1 - Absence of kynurenine 3-monooxygenase reduces mortality of acute viral myocarditis in mice

AU - Kubo, Hisako

AU - Hoshi, Masato

AU - Mouri, Akihiro

AU - Tashita, Chieko

AU - Yamamoto, Yasuko

AU - Nabeshima, Toshitaka

AU - Saito, Kuniaki

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AB - Infection of the encephalomyocarditis virus (EMCV) in mice is an established model for viral myocarditis. Previously, we have demonstrated that indoleamine 2,3-dioxygenase (IDO), an L-tryptophan − kynurenine pathway (KP) enzyme, affects acute viral myocarditis. However, the roles of KP metabolites in EMCV infection remain unclear. Kynurenine 3-monooxygenase (KMO) is one of the key regulatory enzymes, which metabolizes kynurenine to 3-hydroxykynurenine in the KP. Therefore, we examined the role of KMO in acute viral infection by comparing between KMO−/− mice and KMO+/+ mice. KMO deficiency resulted in suppressed mortality after EMCV infection. The number of infiltrating cells and F4/80+ cells in KMO−/− mice was suppressed compared with those in KMO+/+ mice. KMO−/− mice showed significantly increased levels of serum KP metabolites, and induction of KMO expression upon EMCV infection was involved in its effect on mortality through EMCV suppression. Furthermore, KMO−/− mice showed significantly suppression of CCL2, CCL3 and CCL4 on day 2 and CXCL1 on day 4 after infection. These results suggest that increased KP metabolites reduced chemokine production, resulting in suppressed mortality upon KMO knockdown in EMCV infection. KP metabolites may thus provide an effective strategy for treating acute viral myocarditis.

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