The effect of CRP isoforms in combination with oxLDL on the levels of pro-inflammatory cytokines and ROS, produced by U937-derived macrophages

Abstract

Atherosclerosis is a multifactorial inflammatory disease. The mechanisms of atherogenesis are not clear yet; however, it is known that C-reactive protein (CRP) and oxidized low density lipoprotein (oxLDL) play a major role at both early and advanced stages of the disease. The role of CRP is controversial since it was demonstrated to exhibit both pro- and anti-inflammatory effects at the level of the arteries. These antagonistic effects were justified by the discovery of two isoforms of CRP, monomeric (m) and pentameric (p), where the pro-inflammatory and anti-inflammatory effects were attributed to mCRP and pCRP respectively. Another major molecule involved in atherogenesis is the oxLDL that accumulates in macrophages under the intima of the artery hence transforming them into foam cells that form later the atherogenic plaque. OxLDL and CRP may form a complex via phosphatidylcholine and thus delay the progression of atherosclerosis. In our project, we aim to investigate the single and combined effects of mCRP, pCRP and oxLDL on U937-derived macrophages. Therefore, U937-derived macrophages were treated with different combinations of CRPs isoforms with or without oxLDL and the levels of major pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) along with the production of reactive oxygen species (ROS) were determined. TNF-alpha and IL-6 levels were decreased significantly (p < 0.05) by the effect of mCRP and pCRP combined with oxLDL, however, no significant decrease was observed neither in the other combinations nor for the other three parameters tested (IL-1β, IL-8 and ROS).