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 language | English |
|---|---|
| Pages (from-to) | 94-100 |
| Number of pages | 7 |
| Journal | Immunology Letters |
| Volume | 181 |
| DOIs | |
| Publication status | Published - 01-01-2017 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
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Absence of kynurenine 3-monooxygenase reduces mortality of acute viral myocarditis in mice. / Kubo, Hisako; Hoshi, Masato; Mouri, Akihiro; Tashita, Chieko; Yamamoto, Yasuko; Nabeshima, Toshitaka; Saito, Kuniaki.
In: Immunology Letters, Vol. 181, 01.01.2017, p. 94-100.Research output: Contribution to journal › Article
TY - JOUR
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
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85002962666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85002962666&partnerID=8YFLogxK
U2 - 10.1016/j.imlet.2016.11.012
DO - 10.1016/j.imlet.2016.11.012
M3 - Article
C2 - 27889626
AN - SCOPUS:85002962666
VL - 181
SP - 94
EP - 100
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
ER -