Polyinosinic acid induces TNF and NO production as well as NF-κB and AP-1 transcriptional activation in the monocyte-macrophage cell line RAW 264.7

Objective: This study evaluates the poly inosinic acid (poly I)-induced activation in the murine monocyte-macrophage cell line RAW 264.7, which led to an inflammatory phenotype. Material: RAW 264.7, and WEHI 164 cell lines were used. Results: The activation process is characterized by the acquisition of a mature macrophage morphology and the production of inflammatory mediators tumor necrosis factor (TNF) and nitric oxide (NO). The activation by poly I has distinctive features. Thus, poly I induced an increase in nuclear factor kappa B (NF-kappa B) transcriptional activity due to a long-term degradation of inhibitory NF-kappa B (I kappa B) beta while lipopolysaccharide (LPS) induced the degradation of both I kappa B alpha and I kappa B beta. Poly I also induced an increase in activator protein 1 (AP-1) transcriptional activity, possibly due to the activation of the mitogen activated protein kinases (MAPKs) ERK, Jun N terminal kinase (INK) and p38. Dextran sulphate (DS) efficiently inhibited the activation induced by poly I including the production of the inflammatory mediators. Dextran sulphate also inhibited AP-1 and NF-kappa B transcriptional activities in poly I-stimulated cells. RAW 264.7 cells express macrophage scavenger receptor 1 (Msr1) type I and Msr1 type II that are differently up-regulated upon treatment with poly I. Conclusions: The results presented demonstrate that the well-known blocker of scavenger receptors poly I activates macrophages to produce TNF and NO, triggering specific signal transduction pathways.