2. Academic Validation
  3. IL-8 exacerbates CCl4-induced liver fibrosis in human IL-8-expressing mice via the PI3K/Akt/HIF-1α pathway

IL-8 exacerbates CCl4-induced liver fibrosis in human IL-8-expressing mice via the PI3K/Akt/HIF-1α pathway

  • Mol Immunol. 2022 Dec:152:111-122. doi: 10.1016/j.molimm.2022.10.011.
Yuchen Ma 1,  Yanni Bao 1,  Lifang Wu 1,  Yijun Ke 1,  Lina Tan 1,  Huan Ren 1,  Jue Song 1,  Qian Zhang 2,  Yong Jin 3
Affiliations

Affiliations

  • 1 Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China; The Key Laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, Hefei, China; Institute for Liver Diseases of Anhui Medical University, Hefei, China.
  • 2 Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China. Electronic address: [email protected].
  • 3 Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China; The Key Laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, Hefei, China; Institute for Liver Diseases of Anhui Medical University, Hefei, China. Electronic address: [email protected].
PMID: 36327908 DOI: 10.1016/j.molimm.2022.10.011
Abstract

Liver fibrosis is an excessive accumulation of extracellular matrix (ECM) due to chronic liver injury. In recent years, the mechanism of liver fibrosis has been extensively studied. Hepatic stellate cells (HSCs) play an important role in the occurrence and development of liver fibrosis because activated hepatic stellate cells could synthesize a large number of ECM and thus participate in the process of liver fibrosis. Interleukin-8 (IL-8) (deletion in mice) is a versatile chemokine that promotes inflammation and affects cell growth by activating related pathways and plays an important role in the development and progression of a variety of diseases. Notably, the expression level of IL-8 was significantly higher in patients with liver fibrosis, suggesting that it may be related to the pathogenesis of liver fibrosis. In this study, we used hydrodynamic injection to deliver the lentiviral vector LV5-hIL-8 into mice. We found that hIL-8 could aggravate carbon tetrachloride (CCl4)-induced liver fibrosis through the PI3K/Akt/HIF-1α pathway. It is characterized by excessive accumulation of ECM as well as a significant increase in markers of liver injury. In addition, in PDGF-induced HSCs, we also demonstrated that hIL-8 could aggravate ECM accumulation through the PI3K/Akt/HIF-1α pathway. In conclusion, the results of this study on hIL-8 may help to identify potential targets for the clinical treatment of liver fibrosis.

Keywords

Akt; Human interleukin-8; Hypoxia inducible factor 1α; Liver fibrosis; Phosphoinositide 3-kinase.

Figures
Products