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Resolvin D1 prompts inflammation resolution in ACLF rats by increasing the proportion of Treg
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  • Linjun Chen,
  • Yixuan Huang,
  • Yizhen Chen,
  • Jiaxuan Chen,
  • Xueye You,
  • Laiyu Zou,
  • Jiabing Chen,
  • Zhixin Chen,
  • Xiaozhong Wang,
  • Yuehong Huang
Linjun Chen
Fujian Medical University Union Hospital
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Yixuan Huang
Fujian Medical University Union Hospital
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Yizhen Chen
Fujian Medical University Union Hospital
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Jiaxuan Chen
Fujian Medical University Union Hospital
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Xueye You
The First Affiliated Hospital of Xiamen University
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Laiyu Zou
Fujian Medical University Union Hospital
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Jiabing Chen
Fujian Medical University Union Hospital
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Zhixin Chen
Fujian Medical University Union Hospital
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Xiaozhong Wang
Fujian Medical University Union Hospital
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Yuehong Huang
Fujian Medical University Union Hospital

Corresponding Author:[email protected]

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Abstract

Objective: Acute-on-chronic liver failure (ACLF) causes organ system failures and the high mortality, and there is currently a lack of effective means of prevention. The purpose of the study was to explore the therapeutic effects of Resolvin D1 (RvD1) on ACLF rats and its underlying mechanism. Methods: ACLF rat model was constructed by intraperitoneally injecting CCl4 and porcine serum for 6 weeks and then induced acute liver injury by treating with both LPS and D-Galn. The ACLF rats were pretreated with different doses of RvD1 (0.3 or 1 ug/kg) before the acute liver injury. Biochemical analysis, H&E and sirius red staining, flow cytometry assay and real-time PCR were used to assess rat liver histopathological injury, determine the Treg cell frequencies in spleen and the mRNA levels of transcription factors and immunologic cytokines in liver. Results: The necro-inflammatory scores and the serum levels of transaminase significantly increased in ACLF model rats compared to those in normal control rats, with the peak at 8 h. Low-dose of RvD1 could limit necrosis and inflammation and decrease the ALT level of ACLF rats. The degree of damage in ACLF rats was related to the increased mRNA levels of IL-17 and IL-6 in the ACLF rats’ liver and Treg cells reduction in the spleen. Low-dose of RvD1 could protect against liver injury in ACLF rats, as indicated by increasing Treg cell frequency in rats’ spleen and the mRNA levels of Foxp3/RORγ and decreasing the expression of both IL-6 and IL-17. Conclusion: Low-dose of RvD1 plays a protective role in ACLF rats by increasing the proportion of Treg cells. It is the first time to reveal the function of RvD1 in the treatment of ACLF. This work may help us clarify the pathogenesis of ACLF and find effective therapeutic drugs for ACLF.
17 May 2023Submitted to Immunity, Inflammation and Disease
19 May 2023Submission Checks Completed
19 May 2023Assigned to Editor
19 May 2023Review(s) Completed, Editorial Evaluation Pending
25 May 2023Reviewer(s) Assigned
13 Jul 2023Editorial Decision: Revise Major
15 Sep 20231st Revision Received
20 Sep 2023Submission Checks Completed
20 Sep 2023Assigned to Editor
20 Sep 2023Review(s) Completed, Editorial Evaluation Pending
01 Oct 2023Reviewer(s) Assigned
17 Oct 20232nd Revision Received
19 Oct 2023Submission Checks Completed
19 Oct 2023Assigned to Editor
19 Oct 2023Review(s) Completed, Editorial Evaluation Pending
23 Oct 2023Reviewer(s) Assigned
25 Oct 2023Editorial Decision: Accept