2. Academic Validation
  3. Hepatocytes-derived Prdx1 regulates macrophage phenotypes via TLR4 activation in acute liver injury

Hepatocytes-derived Prdx1 regulates macrophage phenotypes via TLR4 activation in acute liver injury

  • Int Immunopharmacol. 2023 Dec 29:127:111439. doi: 10.1016/j.intimp.2023.111439.
Yujing Zhang 1,  Xinru Zhang 1,  Mingxun Zhang 2,  Fanrong Zhang 1,  Tong Chen 1,  Jingjing Zha 1,  Qiying Shen 3,  Dong Wang 4,  Chao Hou 5
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
  • 2 The First Affiliated Hospital of University of Science and Technology of China, China.
  • 3 The First Affiliated Hospital of Anhui Medical University, China. Electronic address: [email protected].
  • 4 School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China. Electronic address: [email protected].
  • 5 School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China. Electronic address: [email protected].
PMID: 38159556 DOI: 10.1016/j.intimp.2023.111439
Abstract

Acute liver injury (ALI) is a significant causative factor for multiple hepatic diseases. The excessive inflammatory response triggers proinflammatory immune cells recruitment, infiltration and differentiation, further contributing to inflammatory injuries in liver. As a proinflammatory factor, circulating Peroxiredoxin 1 (Prdx1) is elevated in ALI patients and mice. In this study, through carbon tetrachloride (CCl4) and cecal puncture and ligation (CLP)-induced liver injury mice model, we found hepatocytes-derived Prdx1 expression was increased in ALI. After AAV8-Prdx1-mediated Prdx1 knockdown, CCl4 and CLP-induced ALI was alleviated, along with the reduced proinflammatory cytokines, suppressed myeloid cells recruitment, decreased proportions of hepatic macrophages and neutrophils, restrained proinflammatory macrophage differentiation and infiltration. Mechanistically, hepatocyte-derived Prdx1 regulated macrophages through paracrine activation of the TLR4 signal. Our data support the immune and inflammatory regulatory role of Prdx1 in ALI pathological process to suggest its potential therapeutic application and clinical value.

Keywords

Acute liver injury; Hepatocyte; Peroxiredoxin 1; Proinflammatory macrophage; Toll like receptor 4.

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