Effect of IL‐17 on pulmonary artery smooth muscle cells and connective tissue disease‐associated pulmonary arterial hypertension

Abstract

Abstract Objective To explore the role of interleukin (IL)‐17 in connective tissue disease‐associated pulmonary arterial hypertension (CTD‐PAH) and to investigate its possible mechanism on pulmonary artery smooth muscle cells (PASMCs). Methods Enzyme‐linked immunosorbent assay (ELISA) were used to compare levels of serum IL‐17 in patients with CTD‐PAH and healthy controls (HCs). After treatment for 3 months, the serum IL‐17 levels were tested in CTD‐PAH. ELISA and immunohistochemistry were used to compare levels of serum IL‐17 and numbers of pulmonary artery IL‐17+ cells, respectively, in a rat model of monocrotaline‐induced PAH and untreated rats. Proliferation, migration, and inflammatory factors expression of PASMCs were assessed after stimulation with different concentrations of IL‐17 for various time periods. Proteins in the mitogen‐activated protein kinase (MAPK) pathway were examined by western blot. Results Levels of IL‐17 were upregulated in patients with CTD‐PAH compared to HCs. After 3 months of treatment, serum IL‐17 levels were downregulated with pulmonary artery pressure amelioration. Moreover, serum IL‐17 levels and numbers of IL‐17+ cells infiltrating lung arterioles were increased in PAH model rats. IL‐17 could dose‐ and time‐dependently promote proliferation and migration of PASMCs as well as time‐dependently induce IL‐6 and intercellular cell adhesion molecule‐1 (ICAM‐1) expression. The levels of MKK6 increased after IL‐17 treatment. Inhibition of MAPK decreased proliferation of PASMCs. Conclusion Levels of IL‐17 may increase in CTD‐PAH, and IL‐17 promotes proliferation, migration, and secretion of IL‐6 and ICAM in PASMCs, respectively, which likely involves the p‐38 MAPK pathway.

Keywords

• connective tissue disease‐associated pulmonary arterial hypertension (CTD‐PAH)
• ICAM
• IL‐17
• MAPK signal pathway
• pulmonary artery smooth muscle cells (PASMCs)