PT  - JOURNAL ARTICLE
AU  - Colin Church
AU  - Ammad Mahmood
AU  - Charlie McSharry
AU  - Damo Xu
AU  - Andrew Peacock
AU  - David Welsh
TI  - A role for ST2/IL-33 signalling in fibroblast proliferation utilising a novel transgenic mouse model of pulmonary hypertension
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - 408
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/408.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/408.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - In this study, we determined if the ST2 receptor and its ligand, interleukin-33 (IL-33) was involved in mouse PAF proliferation and if ST2-/- mice displayed a pulmonary hypertensive phenotype (RVH).Wild type (WT) and ST2 knockout mice (ST2-/-) were used. The effect of IL-33 on proliferation of WT cells was determined by incubation in hypoxia (35mmHg). p38 MAPK, which is involved in fibroblast proliferation, was detected by Western blotting. Right ventricular hypertrophy (RVH) was assessed by measuring the right ventricular wall (RV) and left ventricle with the septum (LV+S).ST2-/- cells proliferated to a greater level compared to WT cells (p<0.01). Proliferation of ST2-/- cells could be reduced by p38 MAPK inhibition (Fig. 1).p38 MAPK was detected in ST2-/- cells but not in WT cells. Proliferation to hypoxia in WT cells could be blocked by IL-33. The ST2-/- mice displayed right ventricular hypertrophy (Fig. 2, p< 0.005).Excessive proliferation of fibroblasts from ST2-/- mice involves p38 MAPK. Proliferation by hypoxia in WT cells can be blocked by IL-33. ST2-/- mice display a pulmonary hypertensive phenotype.