Mechanism of IFN-γ in regulating OPN/Th17 pathway during vascular collagen remodeling of hypertension induced by ANG II

Int J Clin Exp Pathol. 2015 Nov 1;8(11):14433-40. eCollection 2015.

Abstract

More and more researches show that hypertensive vascular remodeling is closely related to the imbalance of immune system in recent years. IFN-γ is natural protein with the function of immune regulation and has resistance effect on vascular remodeling. However, the mechanism of IFN-γ is to be defined. This paper is to explore the mechanism of IFN-γ in regulating OPN/Th17 pathway. In this research, animal models of vascular collagen remodeling were established by inducing hypertensive mice with ANG II. There was no statistical significance when the systolic blood pressures and the percentages of wall thickness/lumen diameter in both groups of WT + AngII + IFN-γ and WT + PBS were compared (P=0.219>0.05, P=0.118>0.05). The concentration of serum precollagen-type I and III and their ratio in WT + AngII + IFN-γ group were decreased after the IFN-γ being given (P<0.01). Expression of OPN within tissue in WT + Ang II group was relatively high, but lowered after treated by IFN-γ. Th17 cell ratio was decreased in WT + AngII + IFN-γ group (P<0.01). Expressions of RORα and RORγt mRNA within Th17 cell were decreased (P<0.01). The content of IL-23 in WT + AngII + IFN-γ group was increased, while IL-10 and TGF-β decreased. It has proved that IFN-γ can regulate the hypertensive vascular collagen remodeling induced by ANG II, lower the systolic pressure and reduce the pathological damage of vascular collagen remodeling and the collagen synthesis. The mechanism may that the differentiation of Th17 is inhibited by suppressing the OPN expression and regulating the secretion of inflammatory cytokines.

Keywords: ANG II; IFN-γ; OPN/Th17; hypertension; vascular collagen remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II*
  • Animals
  • Blood Pressure / drug effects
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Collagen Type I / blood
  • Collagen Type I / metabolism*
  • Collagen Type III / blood
  • Collagen Type III / metabolism*
  • Disease Models, Animal
  • Hypertension / chemically induced
  • Hypertension / genetics
  • Hypertension / immunology
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Inflammation Mediators / metabolism
  • Interferon-gamma / pharmacology*
  • Interleukin-10 / metabolism
  • Interleukin-23 / metabolism
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / metabolism
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Osteopontin / metabolism*
  • Procollagen / blood
  • Procollagen / metabolism*
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / metabolism
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Transforming Growth Factor beta / metabolism
  • Vascular Remodeling / drug effects*

Substances

  • Collagen Type I
  • Collagen Type III
  • IL10 protein, mouse
  • Inflammation Mediators
  • Interleukin-23
  • Nuclear Receptor Subfamily 1, Group F, Member 1
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Procollagen
  • Rora protein, mouse
  • Rorc protein, mouse
  • Spp1 protein, mouse
  • Transforming Growth Factor beta
  • Osteopontin
  • Angiotensin II
  • Interleukin-10
  • Interferon-gamma