Interleukin-33 in pulmonary arterial hypertension

a role in disease pathogenesis?

Nakon Aroonsakool, Dominic Titone, Jinghong Li, Justin Dumouchel, Sandra Lombardi, Nick Kim, David Poch, Timothy Bigby, Fiona Murray

Research output: Contribution to journalAbstract

Abstract

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance that leads to right ventricular failure. PAH can be a primary disease (idiopathic, IPAH) or secondary to conditions such as connective tissue disease. Interleukin-33 (IL-33), which is the ligand for the ST2 receptor, is a cytokine that acts as an alarmin. Since PAH is associated with the infiltration of inflammatory cells and increased cytokines, we aimed to investigate the role of IL-33 in PAH. Using an IL-33 ELISA we found that IL-33 is increased in the serum of PAH patients, in particular IPAH [1798 +/-846 pg/ml (n=6) vs. 24 +/- 13 pg/ml (n=6), p<0.01], compared to control subjects. We found that the mRNA expression of IL-33 is increased ~8-fold in peripheral blood mononuclear cells isolated from PAH-patients and PAH-animal models compared to control; Il-33 is up-regulated in the lung of animal models of PAH. Injury of pulmonary artery endothelial cells (PAEC) released IL-33, thus implying that the increased circulating IL-33 with PAH may occur if the membrane integrity of PAEC is compromised. Administration of IL-33 (500 ng/day intracheally for four days) induced pulmonary arterial remodeling in WT and IL-33 KO mice, but not ST2 KO mice. Our data demonstrate that IL-33 is increased in PAH, which via ST2-dependent signaling, contributes to remodeling of the PA and hence the pathophysiology of the disease.
Original languageEnglish
Article number1090.4
Number of pages1
JournalThe FASEB Journal
Volume28
Issue number1
Publication statusPublished - Apr 2014

Cite this

Aroonsakool, N., Titone, D., Li, J., Dumouchel, J., Lombardi, S., Kim, N., ... Murray, F. (2014). Interleukin-33 in pulmonary arterial hypertension: a role in disease pathogenesis? The FASEB Journal, 28(1), [1090.4].

Interleukin-33 in pulmonary arterial hypertension : a role in disease pathogenesis? / Aroonsakool, Nakon; Titone, Dominic; Li, Jinghong; Dumouchel, Justin; Lombardi, Sandra; Kim, Nick; Poch, David; Bigby, Timothy; Murray, Fiona.

In: The FASEB Journal, Vol. 28, No. 1, 1090.4, 04.2014.

Research output: Contribution to journalAbstract

Aroonsakool, N, Titone, D, Li, J, Dumouchel, J, Lombardi, S, Kim, N, Poch, D, Bigby, T & Murray, F 2014, 'Interleukin-33 in pulmonary arterial hypertension: a role in disease pathogenesis?', The FASEB Journal, vol. 28, no. 1, 1090.4.
Aroonsakool N, Titone D, Li J, Dumouchel J, Lombardi S, Kim N et al. Interleukin-33 in pulmonary arterial hypertension: a role in disease pathogenesis? The FASEB Journal. 2014 Apr;28(1). 1090.4.
Aroonsakool, Nakon ; Titone, Dominic ; Li, Jinghong ; Dumouchel, Justin ; Lombardi, Sandra ; Kim, Nick ; Poch, David ; Bigby, Timothy ; Murray, Fiona. / Interleukin-33 in pulmonary arterial hypertension : a role in disease pathogenesis?. In: The FASEB Journal. 2014 ; Vol. 28, No. 1.
@article{4d768564c2664dcd9cac700f52f3c5ef,
title = "Interleukin-33 in pulmonary arterial hypertension: a role in disease pathogenesis?",
abstract = "Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance that leads to right ventricular failure. PAH can be a primary disease (idiopathic, IPAH) or secondary to conditions such as connective tissue disease. Interleukin-33 (IL-33), which is the ligand for the ST2 receptor, is a cytokine that acts as an alarmin. Since PAH is associated with the infiltration of inflammatory cells and increased cytokines, we aimed to investigate the role of IL-33 in PAH. Using an IL-33 ELISA we found that IL-33 is increased in the serum of PAH patients, in particular IPAH [1798 +/-846 pg/ml (n=6) vs. 24 +/- 13 pg/ml (n=6), p<0.01], compared to control subjects. We found that the mRNA expression of IL-33 is increased ~8-fold in peripheral blood mononuclear cells isolated from PAH-patients and PAH-animal models compared to control; Il-33 is up-regulated in the lung of animal models of PAH. Injury of pulmonary artery endothelial cells (PAEC) released IL-33, thus implying that the increased circulating IL-33 with PAH may occur if the membrane integrity of PAEC is compromised. Administration of IL-33 (500 ng/day intracheally for four days) induced pulmonary arterial remodeling in WT and IL-33 KO mice, but not ST2 KO mice. Our data demonstrate that IL-33 is increased in PAH, which via ST2-dependent signaling, contributes to remodeling of the PA and hence the pathophysiology of the disease.",
author = "Nakon Aroonsakool and Dominic Titone and Jinghong Li and Justin Dumouchel and Sandra Lombardi and Nick Kim and David Poch and Timothy Bigby and Fiona Murray",
year = "2014",
month = "4",
language = "English",
volume = "28",
journal = "The FASEB Journal",
issn = "0892-6638",
publisher = "FEDERATION AMER SOC EXP BIOL",
number = "1",

}

TY - JOUR

T1 - Interleukin-33 in pulmonary arterial hypertension

T2 - a role in disease pathogenesis?

AU - Aroonsakool, Nakon

AU - Titone, Dominic

AU - Li, Jinghong

AU - Dumouchel, Justin

AU - Lombardi, Sandra

AU - Kim, Nick

AU - Poch, David

AU - Bigby, Timothy

AU - Murray, Fiona

PY - 2014/4

Y1 - 2014/4

N2 - Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance that leads to right ventricular failure. PAH can be a primary disease (idiopathic, IPAH) or secondary to conditions such as connective tissue disease. Interleukin-33 (IL-33), which is the ligand for the ST2 receptor, is a cytokine that acts as an alarmin. Since PAH is associated with the infiltration of inflammatory cells and increased cytokines, we aimed to investigate the role of IL-33 in PAH. Using an IL-33 ELISA we found that IL-33 is increased in the serum of PAH patients, in particular IPAH [1798 +/-846 pg/ml (n=6) vs. 24 +/- 13 pg/ml (n=6), p<0.01], compared to control subjects. We found that the mRNA expression of IL-33 is increased ~8-fold in peripheral blood mononuclear cells isolated from PAH-patients and PAH-animal models compared to control; Il-33 is up-regulated in the lung of animal models of PAH. Injury of pulmonary artery endothelial cells (PAEC) released IL-33, thus implying that the increased circulating IL-33 with PAH may occur if the membrane integrity of PAEC is compromised. Administration of IL-33 (500 ng/day intracheally for four days) induced pulmonary arterial remodeling in WT and IL-33 KO mice, but not ST2 KO mice. Our data demonstrate that IL-33 is increased in PAH, which via ST2-dependent signaling, contributes to remodeling of the PA and hence the pathophysiology of the disease.

AB - Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance that leads to right ventricular failure. PAH can be a primary disease (idiopathic, IPAH) or secondary to conditions such as connective tissue disease. Interleukin-33 (IL-33), which is the ligand for the ST2 receptor, is a cytokine that acts as an alarmin. Since PAH is associated with the infiltration of inflammatory cells and increased cytokines, we aimed to investigate the role of IL-33 in PAH. Using an IL-33 ELISA we found that IL-33 is increased in the serum of PAH patients, in particular IPAH [1798 +/-846 pg/ml (n=6) vs. 24 +/- 13 pg/ml (n=6), p<0.01], compared to control subjects. We found that the mRNA expression of IL-33 is increased ~8-fold in peripheral blood mononuclear cells isolated from PAH-patients and PAH-animal models compared to control; Il-33 is up-regulated in the lung of animal models of PAH. Injury of pulmonary artery endothelial cells (PAEC) released IL-33, thus implying that the increased circulating IL-33 with PAH may occur if the membrane integrity of PAEC is compromised. Administration of IL-33 (500 ng/day intracheally for four days) induced pulmonary arterial remodeling in WT and IL-33 KO mice, but not ST2 KO mice. Our data demonstrate that IL-33 is increased in PAH, which via ST2-dependent signaling, contributes to remodeling of the PA and hence the pathophysiology of the disease.

M3 - Abstract

VL - 28

JO - The FASEB Journal

JF - The FASEB Journal

SN - 0892-6638

IS - 1

M1 - 1090.4

ER -