IFNβ and glatiramer acetate trigger different signaling pathways to regulate the IL-1 system in multiple sclerosis

Figures & data

Figure 1 Models of how IFNβ and GA activate PI3Kδ/Akt and MEK/ERK pathways to induce sIL-1Ra production in monocytes. (A) IFNβ binds its specific receptor (IFNAR1-IFNAR2), which induces the activation of MEK2 and the translocation of MEK2 and PI3Kδ to the membrane. The activation of PI3Kδ/Akt pathway leads to sIL-1Ra production in monocytes; Grey kinases and proteins are activated but not implicated in sIL-1Ra production. The type 1IFN canonical STAT1 pathway also is dispensable to sIL-1Ra production.17 (B) GA is recognized by a receptor (cell surface) or a sensor (inside the cell) that transduces signal via activation of both PI3Kδ/Akt and MEK1/2/ERK1/2 pathways. The two pathways then converge to phosphorylate/inactivate GSK3, resulting in the induction of sIL-1Ra production. This scheme is adapted from reference 13.

Molnarfi N, Hyka-Nouspikel N, Gruaz L, Dayer JM, Burger D. The production of IL-1 receptor antagonist in IFN-{beta}-stimulated human monocytes depends on the activation of phosphatidylinositol 3-kinase but not of STAT1. J Immunol 2005; 174:2974 - 2980

 PubMed Web of Science ®Google Scholar

Carpintero R, Brandt KJ, Gruaz L, Molnarfi N, Lalive PH, Burger D. Glatiramer acetate triggers PI3K{delta}/Akt and MEK/ERK pathways to induce IL-1 receptor antagonist in human monocytes. Proc Natl Acad Sci USA 2010; 107:17692 - 17697

 PubMed Web of Science ®Google Scholar