PMID- 30899700
OWN - NLM
STAT- MEDLINE
DCOM- 20191129
LR  - 20200309
IS  - 2235-2988 (Electronic)
IS  - 2235-2988 (Linking)
VI  - 9
DP  - 2019
TI  - Dpep2 Emerging as a Modulator of Macrophage Inflammation Confers Protection 
      Against CVB3-Induced Viral Myocarditis.
PG  - 57
LID - 10.3389/fcimb.2019.00057 [doi]
LID - 57
AB  - Overwhelming cardiac inflammation has been reported to be the pathogenic 
      mechanism of Coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC), while the 
      detailed molecular mechanisms remain unknown. Membrane-bound dipeptidases (MBD, 
      also known as Dpep) have been shown to be involved in inflammatory diseases. 
      However, the clear and direct evidence of their impacts on inflammation is still 
      lacking. In this study, our results revealed that Dpep2 expression was remarkably 
      increased during CVB3 infection, and primarily produced by the cardiac 
      tissue-infiltrating macrophages instead of constitutive cardiomyocytes. 
      Macrophages have been reported to play an important pathological role in driving 
      VMC. Interestingly, macrophage-specific Dpep2 deletion robustly aggravated 
      CVB3-induced cardiac inflammation, evidenced by augmented expression of TNF-alpha, 
      IL-6, and MCP-1 in heart tissue. In addition, Dpep2-deficient bone-marrow derived 
      macrophages (BMDMs) generated more TNF-alpha, IL-6, and MCP-1 after CVB3 stimulation 
      compared with the control BMDMs. Moreover, this suppressive effect of Dpep2 on 
      macrophages relied on its repression on NF-kappaB signaling pathway, but not on its 
      conventional hydrolysate LTE4. Taken together, this study revealed that Dpep2 
      could protect against CVB3-induced VMC by acting as a suppressor of macrophage 
      inflammation. Better understanding how macrophage Dpep2 dampened the cardiac 
      inflammation would provide us with insights for the efficient control of 
      CVB3-induced VMC.
FAU - Yang, Xiaoli
AU  - Yang X
AD  - Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and 
      Medical Sciences, Soochow University, Suzhou, China.
FAU - Yue, Yan
AU  - Yue Y
AD  - Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and 
      Medical Sciences, Soochow University, Suzhou, China.
FAU - Xiong, Sidong
AU  - Xiong S
AD  - Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and 
      Medical Sciences, Soochow University, Suzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190307
PL  - Switzerland
TA  - Front Cell Infect Microbiol
JT  - Frontiers in cellular and infection microbiology
JID - 101585359
RN  - 0 (Immunologic Factors)
RN  - 0 (Membrane Proteins)
RN  - EC 3.4.13.- (Dipeptidases)
RN  - EC 3.4.13.- (Dpep2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Coxsackievirus Infections/immunology/*pathology
MH  - Dipeptidases/deficiency/*metabolism
MH  - Disease Models, Animal
MH  - Enterovirus B, Human/*immunology
MH  - Immunologic Factors/*metabolism
MH  - Macrophages/*immunology
MH  - Membrane Proteins/deficiency/*metabolism
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Myocarditis/immunology/*pathology
PMC - PMC6416667
OTO - NOTNLM
OT  - Dpep2
OT  - NF-kappaB signaling
OT  - coxsackievirus B3 (CVB3)
OT  - macrophages
OT  - viral myocarditis (VMC)
EDAT- 2019/03/23 06:00
MHDA- 2019/11/30 06:00
PMCR- 2019/01/01
CRDT- 2019/03/23 06:00
PHST- 2018/11/30 00:00 [received]
PHST- 2019/02/20 00:00 [accepted]
PHST- 2019/03/23 06:00 [entrez]
PHST- 2019/03/23 06:00 [pubmed]
PHST- 2019/11/30 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fcimb.2019.00057 [doi]
PST - epublish
SO  - Front Cell Infect Microbiol. 2019 Mar 7;9:57. doi: 10.3389/fcimb.2019.00057. 
      eCollection 2019.