Inflammation mediators regulate the LRP-1 Expression in J774 Cells

CESCHIN D, CÁCERES L, SÁNCHEZ MC, ALVAREZ C, CHIABRANDO G.

Igauzú, Misiones. Argentina

Congreso; SAIB; 2004

In atherosclerosis, angiogenesis and tumoral metastasis occur a focal degradation of extracellular matrix components by a broad spectrum of proteinases. Anyway, anti-proteolytic molecules, including proteinase inhibitors and endocytic receptors, play key roles to control these processes. In this sense, LRP-1, a multifunctional endocytic receptor that belongs to the LDL receptor gene family, has been reported to modulate the extracellular proteolytic activity in inflammation. Although it is known that certain inflammatory mediators, including Insulin and Interferon- ã (INF-ã) or bacterial lipopolysacharides (LPS), could affect the biological function of LRP-1, the molecular mechanisms are not clearly understood. In this work we study the regulatory effect of inflammatory mediators and Insulin on LRP-1 expression in J774 macrophage-derived cell line. By western blotting and RT-PCR we demonstrate that both insulin and inflammatory mediators - obtained from a conditioned media of NIH.3T3 fibroblast-derived cell line (MCN) – down-regulate LRP-1 to protein and RNA level. In addition, by immunofluorescence assay we observe that insulin and MCN modify the endocytic activity of LRP-1 in J774 cells. In conclusion in this work we demonstrate that inflammatory mediators can affect the function of LRP-1 by regulating both the expression and endocytosis activity of this receptor.