Corticotropin-releasing hormone attenuates vascular endothelial growth factor release from human HaCaT keratinocytes

Corticotropin-releasing hormone (CRH) is a central component of the local hypothalamic-pituitary-adrenal (HPA) axis, which has a functional equivalent in the skin. To determine whether CRH and its receptor, CRH-R1, modulate the expression of vascular endothelial growth factor (VEGF), which is overexpressed in psoriatic epidermis and plays a causal role in the pathogenesis of psoriasis, we investigated the effect of CRH on the expression of VEGF in a human keratinocyte cell line (HaCaT) and whether this effect is via the mitogen-activated protein kinase (MAPK) signal transduction pathways.

Real-time RT-PCR, ELISA assay and western blot were used in the present study to investigate the expression of VEGF in CRH-treated HaCaT cells.

The mRNA and protein levels of VEGF in CRH-treated HaCaT cells were significantly attenuated. However, this downregulation was abrogated by pretreatment with antalarmin, SB203580 and SP600125; pretreatment with PD98059 did not attenuate the effects of CRH on the expression of VEGF. In addition, CRH treatment induced rapid phosphorylation of p38 MAPK and JNK1/2, and antalarmin, SB203580 and SP600125 inhibited CRH-induced phosphorylation of p38 MAPK and JNK1/2.

CRH might downregulate the expression of VEGF through the CRH-R1 and MAPK (p38 MAPK and JNK1/2) signaling pathways in human HaCaT cells.