Serum neurotensin (NT) is increased in psoriasis and NT induces vascular endothelial growth factor release from human mast cells

Abstract

Summary Background Psoriasis involves skin inflammation that often worsens with stress, but the mechanism of this effect remains obscure. We have shown that corticotrophin- releasing hormone (CRH) is increased in the serum of patients with psoriasis. A peptide, neurotensin (NT), can trigger skin histamine release and augment the ability of CRH to increase skin vascular permeability. Objectives To investigate the serum level of NT, and the expression of genes for NT and NT receptor-1 (NTR-1) in lesional and nonlesional skin of patients with psoriasis, compared with normal controls. Also, to study the effect of NT on human mast cell release of vascular endothelial growth factor (VEGF), which is increased in psoriasis skin. Methods Serum was obtained from patients with psoriasis (n = 56) and controls (n = 33); NT levels were measured with the Milliplex microbead assay. Biopsies were obtained from the lesional and nonlesional skin of patients with chronic plaque psoriasis (n = 40), who had not received any treatment for at least 15 days and were free of any systemic inflammatory diseases. Control skin samples were obtained from healthy subjects (n = 30). Expression of genes for NT and NTR-1 in the skin was evaluated by quantitative reverse transcriptase–polymerase chain reaction. LAD2 human mast cells were stimulated by NT (1 μmol L−1) for 24 h and VEGF was measured by enzyme-linked immunosorbent assay. Results Serum NT was increased in patients with psoriasis, while expression of genes for NT and NTR-1 in lesional skin was decreased compared with controls. NT induced VEGF release from mast cells and was augmented by interleukin-33. Conclusion NT may play a role in psoriasis pathogenesis and its worsening by stress, at least in part through activation of skin mast cells.

Emerging role of neurotensin in regulation of the cardiovascular system

“…including visceral NT-secreting neuroendocrine tumors (neurotensinomas) (Calhoun et al, 2003), gastrointestinal motor abnormalities (Bardella et al, 2000), inflammatory dermatological disorders (Vasiadi et al, 2012(Vasiadi et al, , 2013, neurological disorders (Schimpff et al, 2001), psychiatric disease (Angelidou et al, 2010), and acute sympatho-adrenal activation in shock (Piliponsky et al, 2008) or neonatal asphyxia (Liu et al, 2007). Furthermore, high blood plasma levels of NT precursor (proneurotensin) have been revealed in morbidly obese subjects after bariatric surgery (ChristCrain et al 2006) or gastric bypass operation (Holdstock et al, 2008).…”

“…Another action of NT produced via the mast cell-dependent mechanism, is augmented secretion of the vascular endothelial growth factor (Vasiadi et al, 2012). This effect is likely to contribute to increased epidermal vascularization in inflammatory skin disease.…”

Focal brain inflammation and autism

“…We further showed that NT stimulates mast cell secretion of vascular endothelial growth factor (VEGF) [36], which is also vasodilatory. NT also increases expression of CRH receptor-1 (CRHR-1) [37], activation of which by CRH increases allergic stimulation of human mast cells [38].…”

Stress triggers coronary mast cells leading to cardiac events

“…CRHR-1 gene is expressed on human cultured MC, activation of which induces production of vascular endothelial growth factor (VEGF) 31 . We recently reported that serum CRH was increased in psoriasis (Ps) and atopic dermatitis (AD) 43 patients, and so was NT in Ps 43 and AD patients 44 .…”