TY - JOUR
T1 - Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia
AU - Delgado, René
AU - Carlin, Andrea
AU - Airaghi, Lorena
AU - Demitri, Maria Teresa
AU - Meda, Lucia
AU - Galimberti, Daniela
AU - Baron, Pierluigi
AU - Lipton, James M.
AU - Catania, Anna
PY - 1998/6
Y1 - 1998/6
N2 - Inflammatory processes contribute to neurodegenerative disease, stroke, encephalitis, and other central nervous system (CNS) disorders. Activated microglia are a source of cytokines and other inflammatory agents within the CNS and it is therefore important to control glial function in order to preserve neural cells. Melanocortin peptides are pro-opiomelanocortin- derived amino acid sequences that include α-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti-inflammatory effects. We tested effects of α-MSH (1-13), α- MSH (11-13), and ACTH (1-24) on production of tumor necrosis factor α (TNF- α), interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell line (N9) stimulated with lipopolysaccharide (LPS) plus interferon γ (IFN-γ). Melanocortin peptides inhibited production of these cytokines and NO in a concentration-related fashion, probably by increasing intracellular cAMP. When stimulated with LPS + IFN-γ, microglia increased release of α-MSH. Production of TNF-α, IL-6, and NO was greater in activated microglia after immunoneutralization of endogenous α-MSH. The results suggest that α-MSH is an autocrine factor in microglia. Because melanocortin peptides inhibit production of pro-inflammatory mediators by activated microglia they might be useful in treatment of inflammatory/degenerative brain disorders.
AB - Inflammatory processes contribute to neurodegenerative disease, stroke, encephalitis, and other central nervous system (CNS) disorders. Activated microglia are a source of cytokines and other inflammatory agents within the CNS and it is therefore important to control glial function in order to preserve neural cells. Melanocortin peptides are pro-opiomelanocortin- derived amino acid sequences that include α-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti-inflammatory effects. We tested effects of α-MSH (1-13), α- MSH (11-13), and ACTH (1-24) on production of tumor necrosis factor α (TNF- α), interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell line (N9) stimulated with lipopolysaccharide (LPS) plus interferon γ (IFN-γ). Melanocortin peptides inhibited production of these cytokines and NO in a concentration-related fashion, probably by increasing intracellular cAMP. When stimulated with LPS + IFN-γ, microglia increased release of α-MSH. Production of TNF-α, IL-6, and NO was greater in activated microglia after immunoneutralization of endogenous α-MSH. The results suggest that α-MSH is an autocrine factor in microglia. Because melanocortin peptides inhibit production of pro-inflammatory mediators by activated microglia they might be useful in treatment of inflammatory/degenerative brain disorders.
KW - α-melanocyte-stimulating hormone
KW - Adrenocorticotropic hormone
KW - Cyclic AMP
KW - Interleukin-6
KW - Tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=0031749704&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031749704&partnerID=8YFLogxK
M3 - Article
C2 - 9620667
AN - SCOPUS:0031749704
VL - 63
SP - 740
EP - 745
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 6
ER -