Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis.
Sci Rep
; 6: 34012, 2016 09 21.
Article
in En
| MEDLINE
| ID: mdl-27650973
ABSTRACT
Raynaud's phenomenon is frequently observed in systemic sclerosis (SSc) patients, and cold- or stress-induced norepinephrine (NE) has been speculated to be associated with vasoconstriction. Objective was to elucidate the role of NE in fibrosis in SSc. IL-6 is a potent stimulator of collagen production in fibroblasts. NE enhanced IL-6 production and proliferation more significantly in SSc fibroblasts than in normal fibroblasts. Furthermore, the production of IL-6 and phosphorylation of p38 in SSc fibroblasts was enhanced by adrenergic receptor (AR)ß agonist, isoproterenol, but not ARα agonist, oxymetazoline. ARß blocker, propranolol, inhibited NE-induced IL-6 production and phosphorylation of p38 in SSc fibroblasts. NE-induced IL-6 was significantly inhibited by p38 inhibitor, SB203580, suggesting that NE-induced phosphorylation of p38 via ARß enhances IL-6 production in SSc fibroblasts. NE-induced phosphorylation of ERK1/2 via ARα inhibited IL-6 production in SSc fibroblasts. Combined treatment with NE and endothelin-1 resulted in an additive increase in IL-6 production in SSc fibroblasts. NE-induced IL-6/IL-6 receptor trans-signaling increased the production of collagen type I in SSc fibroblasts, and both propranolol and SB203580 inhibited NE-induced collagen production. These results suggest that cold exposure and/or emotional stress-induced NE might contribute to the skin fibrosis via potentiation of IL-6 production from fibroblasts in SSc.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Scleroderma, Systemic
/
Norepinephrine
/
Fibroblasts
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Sci Rep
Year:
2016
Document type:
Article
Affiliation country:
Japan