Abstract
α-Melanocyte-stimulating hormone (α-MSH) is a potent inhibitory agent in all major forms of inflammation. To identify a potential mechanism of antiinflammatory action of α-MSH, we tested its effects on production of nitric oxide (NO), believed to be a mediator common to all forms of inflammation. We measured NO and α-MSH production in RAW 264.7 cultured routine macrophages stimulated with bacterial lipopolysaccharide and interferon γ. α-MSH inhibited production of NO, as estimated from nitrite production and nitration of endogenous macrophage proteins. This occurred through inhibition of production of NO synthase II protein; steady-state NO synthase II mRNA abundance was also reduced. α-MSH increased cAMP accumulation in RAW cells, characteristic of α-MSH receptors in other cell types. RAW cells also expressed mRNA for the primary α-MSH receptor (melanocortin 1). mRNA for prooplomelanocortin, the precursor molecule of α- MSH, was expressed in RAW cells, and tumor necrosis factor α increased production and release of α-MSH. These results suggest that the proinflammatory cytokine tumor necrosis factor a can induce macrophages to increase production of α-MSH, which then becomes available to act upon melanocortin receptors on the same cells. Such stimulation of melanocortin receptors could modulate inflammation by inhibiting the production of the results suggest that α-MSH is an autocrine factor in macrophages which modulates inflammation by counteracting the effects of proinflammatory cytokines.
| Original language | English |
|---|---|
| Pages (from-to) | 8016-8020 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 92 |
| Issue number | 17 |
| DOIs | |
| Publication status | Published - Aug 15 1995 |
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Keywords
- cAMP
- inflammation
- lipopolysaccharide
- melanocortin receptors
- tumor necrosis factor α
ASJC Scopus subject areas
- Genetics
- General
Cite this
Evidence of autocrine modulation of macrophage nitric oxide synthase by α-melanocyte-stimulating hormone. / Star, Robert A.; Rajora, Nilum; Huang, Jijing; Stock, Renee C.; Catania, Anna; Lipton, J. M.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 17, 15.08.1995, p. 8016-8020.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evidence of autocrine modulation of macrophage nitric oxide synthase by α-melanocyte-stimulating hormone
AU - Star, Robert A.
AU - Rajora, Nilum
AU - Huang, Jijing
AU - Stock, Renee C.
AU - Catania, Anna
AU - Lipton, J. M.
PY - 1995/8/15
Y1 - 1995/8/15
N2 - α-Melanocyte-stimulating hormone (α-MSH) is a potent inhibitory agent in all major forms of inflammation. To identify a potential mechanism of antiinflammatory action of α-MSH, we tested its effects on production of nitric oxide (NO), believed to be a mediator common to all forms of inflammation. We measured NO and α-MSH production in RAW 264.7 cultured routine macrophages stimulated with bacterial lipopolysaccharide and interferon γ. α-MSH inhibited production of NO, as estimated from nitrite production and nitration of endogenous macrophage proteins. This occurred through inhibition of production of NO synthase II protein; steady-state NO synthase II mRNA abundance was also reduced. α-MSH increased cAMP accumulation in RAW cells, characteristic of α-MSH receptors in other cell types. RAW cells also expressed mRNA for the primary α-MSH receptor (melanocortin 1). mRNA for prooplomelanocortin, the precursor molecule of α- MSH, was expressed in RAW cells, and tumor necrosis factor α increased production and release of α-MSH. These results suggest that the proinflammatory cytokine tumor necrosis factor a can induce macrophages to increase production of α-MSH, which then becomes available to act upon melanocortin receptors on the same cells. Such stimulation of melanocortin receptors could modulate inflammation by inhibiting the production of the results suggest that α-MSH is an autocrine factor in macrophages which modulates inflammation by counteracting the effects of proinflammatory cytokines.
AB - α-Melanocyte-stimulating hormone (α-MSH) is a potent inhibitory agent in all major forms of inflammation. To identify a potential mechanism of antiinflammatory action of α-MSH, we tested its effects on production of nitric oxide (NO), believed to be a mediator common to all forms of inflammation. We measured NO and α-MSH production in RAW 264.7 cultured routine macrophages stimulated with bacterial lipopolysaccharide and interferon γ. α-MSH inhibited production of NO, as estimated from nitrite production and nitration of endogenous macrophage proteins. This occurred through inhibition of production of NO synthase II protein; steady-state NO synthase II mRNA abundance was also reduced. α-MSH increased cAMP accumulation in RAW cells, characteristic of α-MSH receptors in other cell types. RAW cells also expressed mRNA for the primary α-MSH receptor (melanocortin 1). mRNA for prooplomelanocortin, the precursor molecule of α- MSH, was expressed in RAW cells, and tumor necrosis factor α increased production and release of α-MSH. These results suggest that the proinflammatory cytokine tumor necrosis factor a can induce macrophages to increase production of α-MSH, which then becomes available to act upon melanocortin receptors on the same cells. Such stimulation of melanocortin receptors could modulate inflammation by inhibiting the production of the results suggest that α-MSH is an autocrine factor in macrophages which modulates inflammation by counteracting the effects of proinflammatory cytokines.
KW - cAMP
KW - inflammation
KW - lipopolysaccharide
KW - melanocortin receptors
KW - tumor necrosis factor α
UR - http://www.scopus.com/inward/record.url?scp=0029143785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029143785&partnerID=8YFLogxK
U2 - 10.1073/pnas.92.17.8016
DO - 10.1073/pnas.92.17.8016
M3 - Article
C2 - 7544012
AN - SCOPUS:0029143785
VL - 92
SP - 8016
EP - 8020
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 17
ER -