Interleukin-13 primes iNO synthase expression induced by LPS in mouse peritoneal macrophages.
Th2 cytokines such as interleukin-13 (IL-13) have both, stimulatory and inhibitory effects on effector functions of macrophages. Reactive nitrogen species are classically induced in Th1 cytokines and/or lipopolysaccharides (LPS) activated macrophages and this response is inhibited by IL-13. In contrast, IL-13 primes macrophages to produce NO in response to LPS when IL-13 treatment happens prior to LPS exposure. This mechanism occurs through a complex signalling pathway, which involves the scavenger receptor CD36, the LPS receptor CD14 and the nuclear receptor PPARgamma. The enhancement of NO production is the consequence of iNOS induction at mRNA and protein levels. The increase of the NO production induced by LPS in IL-13 pre-treated macrophages is found to potentiate the inhibition of Toxoplasma gondii intracellular replication. These results reveal a novel IL-13 signalling pathway that primes the antimicrobial activity of macrophages induced by LPS caused by overexpression of the iNOS-NO axis.
Authier
Hélène
H
Laboratoire des macrophages, Médiateurs de l'Inflammation et Interactions Cellulaires, Université Paul Sabatier Toulouse III, EA2405, INSERM IFR31 BP84225, 31432 Toulouse, Cedex 4, France.
Cassaing
Sophie
S
Coste
Agnès
A
Balard
Patricia
P
Gales
Amandine
A
Berry
Antoine
A
Bans
Valérie
V
Bessières
Marie-Hélène
MH
Pipy
Bernard
B
D000818:Animals; D000890:Anti-Infective Agents; D018955:CD36 Antigens / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018793:Interleukin-13 / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology* / Q000469:parasitology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014122:Toxoplasma / Q000166:cytology / Q000187:drug effects
D000890:Anti-Infective Agents; D018955:CD36 Antigens; D018793:Interleukin-13; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D047495:PPAR gamma; D012333:RNA, Messenger; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II