In:
Journal of Vascular Research, S. Karger AG, Vol. 50, No. 2 ( 2013), p. 145-156
Abstract:
Tumor necrosis factor (TNF)-α can alter tissue repair functions in a variety of cells including endothelial cells. However, the mechanism by which TNF-α mediates these functional changes has not fully been studied. We investigated the role of mitogen-activated protein kinases (MAPKs) on mediating the regulatory effect of TNF-α on the tissue repair functions of human pulmonary artery endothelial cells (HPAECs). TNF-α protected HPAECs from undergoing apoptosis induced by serum and growth factor deprivation, augmented collagen gel contraction, and stimulated wound closure. TNF-α activated c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38. Inhibitors of JNK (SP600125, 5 µ 〈 smlcap 〉 m 〈 /smlcap 〉 ) or ERK1/2 (PD98059, 5 µ 〈 smlcap 〉 m 〈 /smlcap 〉 ) significantly inhibited TNF-α-stimulated cell survival, contraction of collagen gels, and wound closure. In contrast, the p38 inhibitor SB203580 (5 µ 〈 smlcap 〉 m 〈 /smlcap 〉 ) further amplified all of the TNF-α effects on HPAECs. TNF-α specifically activated p38α but not other p38 isoforms and suppression of p38α by an siRNA resulted in further amplification of the TNF-α effect. These results suggest that TNF-α stimulates tissue repair functions of HPAECs, and this may be mediated, at least in part, positively via JNK and ERK1/2, and negatively through p38α. MAPKs may play a role in endothelial cell-mediated tissue repair, especially in an inflammatory milieu where TNF-α is present.
Type of Medium:
Online Resource
ISSN:
1018-1172
,
1423-0135
Language:
English
Publisher:
S. Karger AG
Publication Date:
2013
detail.hit.zdb_id:
1482726-8
