Journal
BIOMED RESEARCH INTERNATIONAL
Volume 2013, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2013/215283
Keywords
-
Funding
- CONACyT, Mexico [104108]
- ICyTDF, Mexico [PIFUTP08-157, 173691, BI11-240]
- CONACyT
Ask authors/readers for more resources
Defence against Leishmania depends upon Th1 inflammatory response and, a major problem in susceptible models, is the turnoff of the leishmanicidal activity of macrophages with IL-10, IL-4, and COX-2 upregulation, as well as immunosuppressive PGE(2), all together inhibiting the respiratory burst. Peroxisome proliferator-activated receptors (PPAR) activation is responsible for macrophages polarization on Leishmania susceptible models where microbicide functions are deactivated. In this paper, we demonstrated that, at least for L. mexicana, PPAR activation, mainly PPAR gamma, induced macrophage activation through their polarization towards M1 profile with the increase of microbicide activity against intracellular pathogen L. mexicana. PPAR activation induced IL-10 downregulation, whereas the production of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and IL-6 remained high. Moreover, PPAR agonists treatment induced the deactivation of cPLA(2)-COX-2-prostaglandins pathway together with an increase in TLR4 expression, all of whose criteriameet the M1 macrophage profile. Finally, parasite burden, in treated macrophages, was lower than that in infected nontreated macrophages, most probably associated with the increase of respiratory burst in these treated cells. Based on the above data, we conclude that PPAR agonists used in this work induces M1 macrophages polarization via inhibition of cPLA(2) and the increase of aggressive microbicidal activity via reactive oxygen species (ROS) production.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available