| First Author | Ballesteros I | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 95 |
| Issue | 4 | Pages | 587-98 |
| PubMed ID | 24338629 | Mgi Jnum | J:211858 |
| Mgi Id | MGI:5576815 | Doi | 10.1189/jlb.0613326 |
| Citation | Ballesteros I, et al. (2014) Rosiglitazone-induced CD36 up-regulation resolves inflammation by PPARgamma and 5-LO-dependent pathways. J Leukoc Biol 95(4):587-98 |
| abstractText | PPARgamma-achieved neuroprotection in experimental stroke has been explained by the inhibition of inflammatory genes, an action in which 5-LO, Alox5, is involved. In addition, PPARgamma is known to promote the expression of CD36, a scavenger receptor that binds lipoproteins and mediates bacterial recognition and also phagocytosis. As phagocytic clearance of neutrophils is a requisite for resolution of the inflammatory response, PPARgamma-induced CD36 expression might help to limit inflammatory tissue injury in stroke, an effect in which 5-LO might also be involved. Homogenates, sections, and cellular suspensions were prepared from brains of WT and Alox5(-/-) mice exposed to distal pMCAO. BMMs were obtained from Lys-M Cre(+) PPARgamma(f/f) and Lys-M Cre(-) PPARgamma(f/f) mice. Stereological counting of double-immunofluorescence-labeled brain sections and FACS analysis of cell suspensions was performed. In vivo and in vitro phagocytosis of neutrophils by microglia/macrophages was analyzed. PPARgamma activation with RSG induced CD36 expression in resident microglia. This process was mediated by the 5-LO gene, which is induced in neurons by PPARgamma activation and at least by one of its products--LXA4--which induced CD36 independently of PPARgamma. Moreover, CD36 expression helped resolution of inflammation through phagocytosis, concomitantly to neuroprotection. Based on these findings, in addition to a direct modulation by PPARgamma, we propose in brain a paracrine model by which products generated by neuronal 5-LO, such as LXA4, increase the microglial expression of CD36 and promote tissue repair in pathologies with an inflammatory component, such as stroke. |
