Abstract
Endothelin-1 (ET-1) plays a pivotal role in vasoconstriction, fibrosis, and inflammation, the key features of systemic sclerosis (SSc). ET-1 receptors (ETA and ETB) are expressed on endothelial cells, smooth muscle cells, and fibroblasts, but their presence on immune cells has not been deeply investigated so far. Endothelin receptors antagonists such as bosentan have beneficial effects on vasoconstriction and fibrosis, but less is known about their potential anti-inflammatory effects. We studied the expression of ET-1 receptors on immune cells (T and B lymphocytes, monocytes, and neutrophils) and the link between ET-1 and inflammation in patients with SSc. We show here that ET-1 exerts a proinflammatory effect in CD4+ T cells, since it induces an increased IFN-γ production; preincubation with antagonists of both receptors reduces IFN-γ production. Moreover, following ET-1 stimulation, neutrophils produce proinflammatory mediators, thus amplifying the effects of activated CD4+ T cells. Our data indicate that ET-1 system is involved in the pathogenesis of inflammation and fibrosis typical of SSc, through the activation of T lymphocytes and neutrophils and the consequent release of proinflammatory and profibrotic cytokines. These findings suggest that dual ET-1 receptors antagonist therapy, besides its effect on vasculopathy, has a profound impact on the immune system favouring antiinflammatory and antifibrogenic effects.
| Original language | English |
|---|---|
| Article number | 147616 |
| Journal | Journal of Immunology Research |
| Volume | 2015 |
| DOIs | |
| Publication status | Published - 2015 |
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ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Endothelin Receptors Expressed by Immune Cells Are Involved in Modulation of Inflammation and in Fibrosis : Relevance to the Pathogenesis of Systemic Sclerosis. / Elisa, Tinazzi; Antonio, Puccetti; Giuseppe, Patuzzo; Alessandro, Barbieri; Giuseppe, Argentino; Federico, Confente; Marzia, Dolcino; Ruggero, Beri; Giacomo, Marchi; Andrea, Ottria; Daniela, Righetti; Mariaelisa, Rampudda; Claudio, Lunardi.
In: Journal of Immunology Research, Vol. 2015, 147616, 2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endothelin Receptors Expressed by Immune Cells Are Involved in Modulation of Inflammation and in Fibrosis
T2 - Relevance to the Pathogenesis of Systemic Sclerosis
AU - Elisa, Tinazzi
AU - Antonio, Puccetti
AU - Giuseppe, Patuzzo
AU - Alessandro, Barbieri
AU - Giuseppe, Argentino
AU - Federico, Confente
AU - Marzia, Dolcino
AU - Ruggero, Beri
AU - Giacomo, Marchi
AU - Andrea, Ottria
AU - Daniela, Righetti
AU - Mariaelisa, Rampudda
AU - Claudio, Lunardi
PY - 2015
Y1 - 2015
N2 - Endothelin-1 (ET-1) plays a pivotal role in vasoconstriction, fibrosis, and inflammation, the key features of systemic sclerosis (SSc). ET-1 receptors (ETA and ETB) are expressed on endothelial cells, smooth muscle cells, and fibroblasts, but their presence on immune cells has not been deeply investigated so far. Endothelin receptors antagonists such as bosentan have beneficial effects on vasoconstriction and fibrosis, but less is known about their potential anti-inflammatory effects. We studied the expression of ET-1 receptors on immune cells (T and B lymphocytes, monocytes, and neutrophils) and the link between ET-1 and inflammation in patients with SSc. We show here that ET-1 exerts a proinflammatory effect in CD4+ T cells, since it induces an increased IFN-γ production; preincubation with antagonists of both receptors reduces IFN-γ production. Moreover, following ET-1 stimulation, neutrophils produce proinflammatory mediators, thus amplifying the effects of activated CD4+ T cells. Our data indicate that ET-1 system is involved in the pathogenesis of inflammation and fibrosis typical of SSc, through the activation of T lymphocytes and neutrophils and the consequent release of proinflammatory and profibrotic cytokines. These findings suggest that dual ET-1 receptors antagonist therapy, besides its effect on vasculopathy, has a profound impact on the immune system favouring antiinflammatory and antifibrogenic effects.
AB - Endothelin-1 (ET-1) plays a pivotal role in vasoconstriction, fibrosis, and inflammation, the key features of systemic sclerosis (SSc). ET-1 receptors (ETA and ETB) are expressed on endothelial cells, smooth muscle cells, and fibroblasts, but their presence on immune cells has not been deeply investigated so far. Endothelin receptors antagonists such as bosentan have beneficial effects on vasoconstriction and fibrosis, but less is known about their potential anti-inflammatory effects. We studied the expression of ET-1 receptors on immune cells (T and B lymphocytes, monocytes, and neutrophils) and the link between ET-1 and inflammation in patients with SSc. We show here that ET-1 exerts a proinflammatory effect in CD4+ T cells, since it induces an increased IFN-γ production; preincubation with antagonists of both receptors reduces IFN-γ production. Moreover, following ET-1 stimulation, neutrophils produce proinflammatory mediators, thus amplifying the effects of activated CD4+ T cells. Our data indicate that ET-1 system is involved in the pathogenesis of inflammation and fibrosis typical of SSc, through the activation of T lymphocytes and neutrophils and the consequent release of proinflammatory and profibrotic cytokines. These findings suggest that dual ET-1 receptors antagonist therapy, besides its effect on vasculopathy, has a profound impact on the immune system favouring antiinflammatory and antifibrogenic effects.
UR - http://www.scopus.com/inward/record.url?scp=84930965551&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930965551&partnerID=8YFLogxK
U2 - 10.1155/2015/147616
DO - 10.1155/2015/147616
M3 - Article
AN - SCOPUS:84930965551
VL - 2015
JO - Journal of Immunology Research
JF - Journal of Immunology Research
SN - 2314-8861
M1 - 147616
ER -