Interplay Between Inflammatory-immune and Interleukin-17 Signalings Plays a Cardinal Role on Liver Ischemia-reperfusion Injury—Synergic Effect of IL-17Ab, Tacrolimus and ADMSCs on Rescuing the Liver Damage

Sheung Fat Ko, Yi Chen Li, Pei Lin Shao, John Y. Chiang, Pei Hsun Sung, Yi Ling Chen*, Hon Kan Yip*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

Background: This study tested the hypothesis that inflammatory and interleukin (IL)-17 signalings were essential for acute liver ischemia (1 h)-reperfusion (72 h) injury (IRI) that was effectively ameliorated by adipose-derived mesenchymal stem cells (ADMSCs) and tacrolimus. Methods: Adult-male SD rats (n = 50) were equally categorized into groups 1 (sham-operated-control), 2 (IRI), 3 [IRI + IL-17-monoclonic antibody (Ab)], 4 (IRI + tacrolimus), 5 (IRI + ADMSCs) and 6 (IRI + tacrolimus-ADMSCs) and liver was harvested at 72 h. Results: The main findings included: (1) circulatory levels: inflammatory cells, immune cells, and proinflammatory cytokines as well as liver-damage enzyme at the time point of 72 h were highest in group 2, lowest in group 1 and significantly lower in group 6 than in groups 3 to 5 (all p < 0.0001), but they did not differ among these three latter groups; (2) histopathology: the liver injury score, fibrosis, inflammatory and immune cell infiltration in liver immunity displayed an identical pattern of inflammatory cells among the groups (all p < 0.0001); and (3) protein levels: upstream and downstream inflammatory signalings, oxidative-stress, apoptotic and mitochondrial-damaged biomarkers exhibited an identical pattern of inflammatory cells among the groups (all p < 0.0001). Conclusion: Our results obtained from circulatory, pathology and molecular-cellular levels delineated that acute IRI was an intricate syndrome that elicited complex upstream and downstream inflammatory and immune signalings to damage liver parenchyma that greatly suppressed by combined tacrolimus and ADMSCs therapy.

Original languageEnglish
Pages (from-to)2852-2868
Number of pages17
JournalStem Cell Reviews and Reports
Volume19
Issue number8
DOIs
StatePublished - 11 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

  • Adipose-derived mesenchymal stem cells
  • Hepatic ischemia-reperfusion injury
  • Immune response
  • Inflammation
  • Interleukin-17
  • Tacrolimus

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