PMID- 37634445
OWN - NLM
STAT- Publisher
LR  - 20231017
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 124
IP  - Pt A
DP  - 2023 Nov
TI  - Ruxolitinib ameliorated coxsackievirus B3-induced acute viral myocarditis by 
      suppressing the JAK-STAT pathway.
PG  - 110797
LID - S1567-5769(23)01122-0 [pii]
LID - 10.1016/j.intimp.2023.110797 [doi]
AB  - BACKGROUND: Accumulating evidences have demonstrated that overwhelming 
      inflammation occurs in the process of Coxsackievirus B3 (CVB3)-induced acute 
      viral myocarditis (AVM). No specific therapy is available. More than an effective 
      Janus-associated kinase (JAK) inhibiter, ruxolitinib exerts a critical role in 
      the inflammatory diseases. In this study, we investigated the potential effect of 
      ruxolitinib on CVB3-induced acute viral myocarditis. METHOD: In vivo, BALB/c mice 
      were intraperitoneally injected of CVB3, treated of a successive gavage of 
      ruxolitinib for seven days, and subjected to a series of analysis. In vitro, 
      primary bone marrow-derived macrophages (BMDMs) and cardiac fibroblasts were 
      isolated, cultured, treated, harvested and finally detected. RESULTS: In vivo, 
      acute viral myocarditis was successfully induced by the injection of CVB3 
      characterized by impaired cardiac function, predominant infiltration of 
      inflammatory cells, necroptosis of myocardium, great increase of cardiac troponin 
      I (cTnI) and cytokine levels, replication of CVB3, and excessive activation of 
      JAK-STAT pathways. Oral administration of ruxolitinib suppressed the activation 
      of JAK-STAT pathway in a dosage-dependent way, lessened the infiltration of 
      inflammatory cells and necroptosis of myocardium, reduced the levels of cTnI and 
      cytokines, and finally alleviated CVB3-induced cardiac dysfunction, with the 
      reduced production of type I interferon and no promising effect on the 
      replication of CVB3. In vitro, the treatment of ruxolitinib inhibited the 
      activation of JAK-STAT pathway and increase of multiple cytokines mRNA levels in 
      BMDMs and had no protective effect against CVB3 replication in cardiac 
      fibroblasts. CONCLUSIONS: Our study suggested that ruxolitinib ameliorated 
      CVB3-induced AVM by inhibiting the activation of JAK-STAT pathway, infiltration 
      of inflammatory cells and necroptosis of myocardium, which may provide a novel 
      strategy for AVM therapy.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Chen, Liang
AU  - Chen L
AD  - Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030, China.
FAU - Zhu, Meng-Ying
AU  - Zhu MY
AD  - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan 430030, 
      China.
FAU - Wang, Gao-Xiang
AU  - Wang GX
AD  - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 
      430030, China.
FAU - Lu, Li-Li
AU  - Lu LL
AD  - Institute of Pharmaceutical Innovation, College of Medicine, Wuhan University of 
      Science and Technology, Wuhan 430065, Hubei, China.
FAU - Lin, Li
AU  - Lin L
AD  - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan 430030, 
      China. Electronic address: linli@tjh.tjmu.edu.cn.
FAU - Lei, Lei
AU  - Lei L
AD  - Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan 430030, 
      China. Electronic address: lltongji2015@163.com.
FAU - Wu, Ting
AU  - Wu T
AD  - Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030, China. 
      Electronic address: wuting@tjh.tjmu.edu.
LA  - eng
PT  - Journal Article
DEP - 20230825
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
SB  - IM
OTO - NOTNLM
OT  - Acute viral myocarditis
OT  - Coxsackievirus B3
OT  - Inflammation
OT  - Janus-associated kinase
OT  - Ruxolitinib
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/08/28 00:41
MHDA- 2023/08/28 00:41
CRDT- 2023/08/27 18:08
PHST- 2023/02/10 00:00 [received]
PHST- 2023/08/02 00:00 [revised]
PHST- 2023/08/11 00:00 [accepted]
PHST- 2023/08/28 00:41 [pubmed]
PHST- 2023/08/28 00:41 [medline]
PHST- 2023/08/27 18:08 [entrez]
AID - S1567-5769(23)01122-0 [pii]
AID - 10.1016/j.intimp.2023.110797 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Nov;124(Pt A):110797. doi: 
      10.1016/j.intimp.2023.110797. Epub 2023 Aug 25.