Pravastatin Sodium Attenuated TREM-1-mediated Inflammation In Human Peripheral Blood Mononuclear Cells

Background Chronic obstructive pulmonary disease(COPD)is considered to be a systemic inflammatory disease.Myeloid cell-triggering receptor-1(TREM-1)belongs to the IgG-type immunoglobulin superfamily receptor.It is mainly expressed on the membrane surface of neutrophils,monocytes and macrophages.In the presence of microbial products,TREM-1 can amplify toll-like and nod-like receptor-mediated inflammatory responses,promote activation and release of chemokines and cytokines,prolong the survival time of macrophages,and eventually lead to an excessive inflammatory response.Like many membrane-bound receptors,TREM-1 also exists in human body fluids in a soluble form.Studies shown that sTREM-1 in human fluids may be a potential marker for an early diagnosis and prognosis of certain infectious diseases.Statins are 3-hydroxymethyl-3-glutaryl coenzyme A reductase inhibitor,which have been ordinarily used as a lipid-lowering therapy for hyperlipidemia,especially hypercholesterolemia.Beside their lipid-lowering effects,a remarkable anti-inflammatory effect has been reported by many researches.At present,the anti-inflammatory effects of statins have been repeatedly confirmed in human and animal lung inflammatory diseases.However,there is no research on whether statins can inhibit TREM-1 mediated inflammatory response.Objective This study aims to investigate the effects of pravastatin sodium on TREM-1-medieted inflammation in PBMCs as well as the potential mechanism.Methods PBMCs were isolated from peripheral blood of patients with chronic obstructive pulmonary disease,treated with different concentrations of pravastatin sodium,and determined for drug concentrations that would allow cell viability to exceed 90%.The cells were treated with LPS.Different concentrations of pravastatin sodium with or without LR-12,a TREM-1 inhibitor,were added.TREM-1 expression was determined by qRT-PCR,sTREM-1,IL-6,TNF-? levels were detected by ELISA.The NF-?B signaling pathway-related proteins p-p65 and p-I?B? were detected by Western blot assay.Results Pravastatin sodium significantly inhibited LPS-stimulated the expression of TREM-1.As the concentrations of pravastatin sodium increased,the inhibitory effects gradually increased.When the concentration of pravastatin sodium was 100?M,the degree of inhibition reached the greatest;sTREM-1,IL-6 and TNF-? levels in the cell culture supernatants detected by ELISA showed a similar tendency;The inhibition effects were not enhanced when cells were treated with pravastatin sodium and LR-12 simultaneously;Pravastatin sodium significantly decreased LPS-induced p-p65 and p-I?B? levels.As the concentrations of pravastatin sodium increased,the inhibitory effects gradually increased.When the concentration of pravastatin sodium was 100?M,the degree of inhibition reached the greatest.Conclusions Pravastatin sodium could inhibit TREM-1-medieted inflammation in PBMCs and the activation of NF-?B signaling pathway was involved.