Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E(2) and cytokines.
OBJECTIVE
To investigate the effect of short-chain fatty acids (SCFAs) on production of prostaglandin E(2) (PGE(2)), cytokines and chemokines in human monocytes.


METHODS
Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative real-time polymerase chain reaction. The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells (PBMC) was studied by measuring PGE(2), cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws.


RESULTS
Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE(2) and that this effect can be enhanced in the presence of lipopolysaccharide (LPS). In addition, we demonstrate that PGE(2) production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 (MCP-1) production and LPS-induced interleukin-10 (IL-10) production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE(2), MCP-1 and IL-10 after SCFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-alpha and interferon-gamma in human PBMC. Finally, we show that SCFAs and LPS can induce PGE(2) production in vivo by intraplantar injection into rat paws (P < 0.01).


CONCLUSIONS
SCFAs can have distinct antiinflammatory activities due to their regulation of PGE(2), cytokine and chemokine release from human immune cells.
Cox
Mary Ann
MA
Department of Tumor Biology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Jackson
James
J
Stanton
Michaela
M
Rojas-Triana
Alberto
A
Bober
Loretta
L
Laverty
Maureen
M
Yang
Xiaoxin
X
Zhu
Feng
F
Liu
Jianjun
J
Wang
Suke
S
Monsma
Frederick
F
Vassileva
Galya
G
Maguire
Maureen
M
Gustafson
Eric
E
Bayne
Marvin
M
Chou
Chuan-Chu
CC
Lundell
Daniel
D
Jenh
Chung-Her
CH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D005232:Fatty Acids, Volatile; D008070:Lipopolysaccharides; D016753:Interleukin-10; D015232:Dinoprostone; D002118:Calcium