Functional analysis and regulation mechanism of interferon gamma in macrophages of large yellow croaker (Larimichthys crocea)

Int J Biol Macromol. 2022 Jan 1:194:153-162. doi: 10.1016/j.ijbiomac.2021.11.183. Epub 2021 Dec 2.

Abstract

Interferon gamma (IFN-γ) is a widely expressed cytokine that has potent antiviral and immunomodulatory effects. The expression and bioactivity of IFN-γ have been reported in several fish species. However, the molecular mechanism mediated by IFN-γ in fish macrophages has not been completely elucidated. This study used the macrophage cell line to investigate the functional activities and regulation mechanism of large yellow croaker IFN-γ (LcIFN-γ). Herein, the mRNA expression of Lcifn-γ was significantly upregulated in macrophages after LPS and poly(I:C) treatment. Recombinant LcIFN-γ protein (rLcIFN-γ) significantly enhanced the phagocytic ability and respiratory burst activity of macrophages. Meanwhile, rLcIFN-γ induced M1 phenotype polarization of macrophages with the upregulated expressions of pro-inflammatory gene. Moreover, rLcIFN-γ upregulated the IFN-stimulated genes (ISGs) expression and activated JAK (Janus tyrosine kinases)-STAT (signal transducer and activator of transcription) signaling pathway by causing the phosphorylation of JAK1 and STAT1Tyr701. Furthermore, the promoter activity of IFN-regulatory factor 1 (IRF1) was significantly upregulated by the phosphorylated transcription factor STAT1 through binding to its promoter region. In addition to the classical JAK-STAT pathway, rLcIFN-γ also activated multiple distinct signaling cascades such as mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) pathways. Overall, this study indicated the powerful effects of LcIFN-γ on macrophage activation of large yellow croaker and its molecular mechanism.

Keywords: Interferon gamma; Large yellow croaker; Macrophage.

MeSH terms

  • Animals
  • Gene Expression
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Janus Kinases / metabolism
  • Lipopolysaccharides / immunology
  • Macrophage Activation / immunology
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Perciformes / physiology*
  • Phagocytosis
  • Protein Binding
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • STAT Transcription Factors / metabolism

Substances

  • Lipopolysaccharides
  • Recombinant Proteins
  • STAT Transcription Factors
  • Interferon-gamma
  • Janus Kinases