PMID- 38391023
OWN - NLM
STAT- Publisher
LR  - 20240223
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Linking)
DP  - 2024 Feb 23
TI  - Interleukin-6 trans-signaling regulates monocyte chemoattractant protein-1 
      production in immune-mediated necrotizing myopathy.
LID - keae118 [pii]
LID - 10.1093/rheumatology/keae118 [doi]
AB  - OBJECTIVE: Immune-mediated necrotizing myopathy (IMNM) is pathologically 
      characterized by diffuse myofiber necrosis and regeneration, myophagocytosis, and 
      a sparse inflammatory infiltrate. The monocyte chemoattractant protein-1 (MCP-1) 
      is a key chemokine that regulates monocyte/macrophage infiltration into injured 
      tissues. The interleukin-6 (IL-6) signalling in the induction of MCP-1 expression 
      has not been investigated in IMNM. METHODS: MCP-1 expression in muscle specimens 
      was assessed using immunohistochemistry and real-time quantitative polymerase 
      chain reaction (RT-qPCR). Levels of multiple serological cytokines were evaluated 
      using the Meso Scale Discovery electrochemiluminescence system. Flow cytometry, 
      RT-qPCR, enzyme-linked immunosorbent assay, western blot, dual-luciferase 
      reporter assays, and chromatin immunoprecipitation-qPCR were performed to explore 
      the effects of IL-6 signalling on MCP-1 production in human myoblasts. RESULTS: 
      MCP-1 was scattered and was positively expressed within myofibers and a few 
      inflammatory cells in the muscles of patients with IMNM. Sarcoplasmic MCP-1 
      expression significantly correlated with myonecrosis, myoregeneration, and 
      inflammatory infiltration. Serum MCP-1, IL-6, and the soluble form of the IL-6 
      receptor (sIL-6R) were elevated in patients with IMNM compared with controls. 
      Serological MCP-1 levels were significantly associated with serum IL-6 expression 
      and clinical disease severity in IMNM patients. The IL-6/sIL-6R complex induced 
      MCP-1 expression via the signal transducer and activator of transcription 3 
      (STAT3) pathway in human myoblasts. Mechanistically, phospho-STAT3 was enriched 
      in the MCP-1 promoter region and promoted the transcription. CONCLUSION: IL-6 
      trans-signalling may contribute to the immunopathogenesis of IMNM by augmenting 
      inflammation through regulation of MCP-1 expression in IMNM.
CI  - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the 
      British Society for Rheumatology. All rights reserved. For permissions, please 
      email: journals.permissions@oup.com.
FAU - Ma, Xue
AU  - Ma X
AD  - Department of Neurology, The First Affiliated Hospital of Xi'an Jiao Tong 
      University, Xi'an, 710000, China.
AD  - Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430030, China.
FAU - Gao, Hua-Jie
AU  - Gao HJ
AD  - Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430030, China.
FAU - Ge, Hui-Zhen
AU  - Ge HZ
AD  - Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430030, China.
FAU - Zhang, Qing
AU  - Zhang Q
AD  - Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430030, China.
FAU - Bu, Bi-Tao
AU  - Bu BT
AUID- ORCID: 0000-0003-3686-4153
AD  - Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430030, China.
LA  - eng
PT  - Journal Article
DEP - 20240223
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
SB  - IM
OTO - NOTNLM
OT  - immune-mediated necrotizing myopathies
OT  - interleukin-6 trans-signaling
OT  - macrophages
OT  - monocyte chemoattractant protein-1
OT  - signal transducer and activator of transcription 3
EDAT- 2024/02/23 12:42
MHDA- 2024/02/23 12:42
CRDT- 2024/02/23 08:04
PHST- 2023/08/23 00:00 [received]
PHST- 2024/01/06 00:00 [revised]
PHST- 2024/02/12 00:00 [accepted]
PHST- 2024/02/23 12:42 [medline]
PHST- 2024/02/23 12:42 [pubmed]
PHST- 2024/02/23 08:04 [entrez]
AID - 7613067 [pii]
AID - 10.1093/rheumatology/keae118 [doi]
PST - aheadofprint
SO  - Rheumatology (Oxford). 2024 Feb 23:keae118. doi: 10.1093/rheumatology/keae118.