1-Methylnicotinamide and nicotinamide: two related anti-inflammatory agents that differentially affect the functions of activated macrophages.
BACKGROUND
1-Methylnicotinamide (MNA), a major metabolite of nicotinamide (NA), is known to exert anti-inflammatory effects in vivo. Treatment of inflammatory skin diseases by topical application of MNA provides certain advantages over the use of NA. However, in contrast to NA, the molecular mechanisms of the anti-inflammatory properties of MNA are not well known. In this study the influence of exogenous MNA and NA in vivo on the generation of inflammatory mediators by macrophages (Mvarphi) was investigated.


METHODS
Peritoneal Mvarphi of CBA/J mice were activated in vitro with lipopolysaccharide and incubated with MNA or NA. The effect of these compounds on biological functions of Mvarphi was measured by evaluation of the production of reactive oxygen species (ROS) by luminol-dependent chemiluminescence, cytokines and prostaglandin E(2) (PGE(2)) by ELISA, and nitric oxide (NO) by the Griess method. Moreover, the expressions of inducible NO synthase and cyclooxygenase-2 were measured by Western blotting.


RESULTS
It was shown that at non-cytotoxic concentrations, NA inhibits the production of a variety of pro-inflammatory agents, such as tumor necrosis factor alpha, interleukin 6, NO, PGE(2), and the generation of ROS. In contrast to NA, exogenous MNA inhibited only the generation of ROS, while its effect on the synthesis of other mediators was negligible.


CONCLUSIONS
These results indicate that the anti-inflammatory properties of MNA demonstrated previously in vivo do not depend on its capacity to suppress the functions of immune cells, but more likely may be related to its action on vascular endothelium. The authors suggest that the limited permeability for exogenous MNA, in contrast to that for NA, may be responsible for its lack of suppressor activity against Mvarphi.
Biedroń
Rafał
R
Department of Immunology, Jagiellonian University College of Medicine, Czysta 18, 31-121 Kraków, Poland.
Ciszek
Marta
M
Tokarczyk
Marianna
M
Bobek
Małgorzata
M
Kurnyta
Maria
M
Słominska
Ewa M
EM
Smoleński
Ryszard T
RT
Marcinkiewicz
Janusz
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D017382:Reactive Oxygen Species; D009536:Niacinamide; D009569:Nitric Oxide; D015232:Dinoprostone; C024058:N(1)-methylnicotinamide