Abstract
Natural melanocortin peptides exert broad effects on the host and they have remarkable therapeutic potential. However, successful use of melanocortins as therapeutic agents depends on the design of molecules that have more stable pharmacological profiles. The synthetic peptide (CKPV)2, based on the C-terminal sequence of α-melanocyte stimulating hormone (α-MSH), has anti-tumor necrosis factor-α (TNF-α) effects in vitro and in vivo and is a promising candidate to treat inflammation. Because neutrophil activity is a major target for anti-inflammatory therapies, we determined whether (CKPV)2 modulates human neutrophil functions in vitro. Incubation of freshly-separated human neutrophils with 10-12-10-6 M (CKPV)2 significantly inhibited activities relevant to the inflammatory reaction. Neutrophil migration toward the two chemoattractants interleukin 8 (IL-8) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) was significantly inhibited by (CKPV)2. (CKPV)2 also inhibited reactive oxygen intermediate (ROI) production induced by phorbol 12-myristate 13-acetate (PMA), but not that induced by fMLP. Because these effects of (CKPV)2 were abolished by the adenylyl cyclase inhibitor 2′,5′-dideoxyadenosine (ddAdo), they appear to be cAMP-dependent. Finally, the peptide reduced lipopolysaccharide (LPS)-stimulated expression of TNF-α, interleukin-1β (IL-1β), interleukin-8 (IL-8), and intercellular adhesion molecule 1 (ICAM-1), as well as TNF-α protein release in cell supernatants. The data indicate that (CKPV)2 modulates broad cAMP-dependent, anti-inflammatory pathways in human neutrophils.
| Original language | English |
|---|---|
| Pages (from-to) | 2016-2022 |
| Number of pages | 7 |
| Journal | Peptides |
| Volume | 28 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2007 |
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Keywords
- α-Melanocyte stimulating hormone (α-MSH)
- (CKPV)
- Chemotaxis
- Human neutrophils
- Lipopolysaccharide (LPS)
- Melanocortin peptides
- Respiratory burst
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Physiology
- Cellular and Molecular Neuroscience
Cite this
The synthetic melanocortin (CKPV)2 exerts broad anti-inflammatory effects in human neutrophils. / Capsoni, Franco; Ongari, Annamaria; Colombo, Gualtiero; Turcatti, Flavia; Catania, Anna.
In: Peptides, Vol. 28, No. 10, 10.2007, p. 2016-2022.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The synthetic melanocortin (CKPV)2 exerts broad anti-inflammatory effects in human neutrophils
AU - Capsoni, Franco
AU - Ongari, Annamaria
AU - Colombo, Gualtiero
AU - Turcatti, Flavia
AU - Catania, Anna
PY - 2007/10
Y1 - 2007/10
N2 - Natural melanocortin peptides exert broad effects on the host and they have remarkable therapeutic potential. However, successful use of melanocortins as therapeutic agents depends on the design of molecules that have more stable pharmacological profiles. The synthetic peptide (CKPV)2, based on the C-terminal sequence of α-melanocyte stimulating hormone (α-MSH), has anti-tumor necrosis factor-α (TNF-α) effects in vitro and in vivo and is a promising candidate to treat inflammation. Because neutrophil activity is a major target for anti-inflammatory therapies, we determined whether (CKPV)2 modulates human neutrophil functions in vitro. Incubation of freshly-separated human neutrophils with 10-12-10-6 M (CKPV)2 significantly inhibited activities relevant to the inflammatory reaction. Neutrophil migration toward the two chemoattractants interleukin 8 (IL-8) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) was significantly inhibited by (CKPV)2. (CKPV)2 also inhibited reactive oxygen intermediate (ROI) production induced by phorbol 12-myristate 13-acetate (PMA), but not that induced by fMLP. Because these effects of (CKPV)2 were abolished by the adenylyl cyclase inhibitor 2′,5′-dideoxyadenosine (ddAdo), they appear to be cAMP-dependent. Finally, the peptide reduced lipopolysaccharide (LPS)-stimulated expression of TNF-α, interleukin-1β (IL-1β), interleukin-8 (IL-8), and intercellular adhesion molecule 1 (ICAM-1), as well as TNF-α protein release in cell supernatants. The data indicate that (CKPV)2 modulates broad cAMP-dependent, anti-inflammatory pathways in human neutrophils.
AB - Natural melanocortin peptides exert broad effects on the host and they have remarkable therapeutic potential. However, successful use of melanocortins as therapeutic agents depends on the design of molecules that have more stable pharmacological profiles. The synthetic peptide (CKPV)2, based on the C-terminal sequence of α-melanocyte stimulating hormone (α-MSH), has anti-tumor necrosis factor-α (TNF-α) effects in vitro and in vivo and is a promising candidate to treat inflammation. Because neutrophil activity is a major target for anti-inflammatory therapies, we determined whether (CKPV)2 modulates human neutrophil functions in vitro. Incubation of freshly-separated human neutrophils with 10-12-10-6 M (CKPV)2 significantly inhibited activities relevant to the inflammatory reaction. Neutrophil migration toward the two chemoattractants interleukin 8 (IL-8) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) was significantly inhibited by (CKPV)2. (CKPV)2 also inhibited reactive oxygen intermediate (ROI) production induced by phorbol 12-myristate 13-acetate (PMA), but not that induced by fMLP. Because these effects of (CKPV)2 were abolished by the adenylyl cyclase inhibitor 2′,5′-dideoxyadenosine (ddAdo), they appear to be cAMP-dependent. Finally, the peptide reduced lipopolysaccharide (LPS)-stimulated expression of TNF-α, interleukin-1β (IL-1β), interleukin-8 (IL-8), and intercellular adhesion molecule 1 (ICAM-1), as well as TNF-α protein release in cell supernatants. The data indicate that (CKPV)2 modulates broad cAMP-dependent, anti-inflammatory pathways in human neutrophils.
KW - α-Melanocyte stimulating hormone (α-MSH)
KW - (CKPV)
KW - Chemotaxis
KW - Human neutrophils
KW - Lipopolysaccharide (LPS)
KW - Melanocortin peptides
KW - Respiratory burst
UR - http://www.scopus.com/inward/record.url?scp=34548802959&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548802959&partnerID=8YFLogxK
U2 - 10.1016/j.peptides.2007.08.001
DO - 10.1016/j.peptides.2007.08.001
M3 - Article
C2 - 17850921
AN - SCOPUS:34548802959
VL - 28
SP - 2016
EP - 2022
JO - Peptides
JF - Peptides
SN - 0196-9781
IS - 10
ER -