Biochemical and Biophysical Research Communications
Pravastatin sodium attenuated TREM-1-mediated inflammation in human peripheral blood mononuclear cells
Introduction
Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease, characterized by progressive development of the irreversible airway inflammation, airflow limitation, and declined lung function. The pathogenesis of COPD has not been fully elucidated while chronic inflammation in the lower airway was considered to be crucial. Studies showed that neutrophils, monocytes, lymphocytes, and macrophages are involved in the inflammation [1]. These cells release various inflammatory mediators such as interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) to attract more inflammatory cells from the circulation, enhance the inflammatory process, and induce structural changes. Peripheral blood mononuclear cells (PBMCs) consist of monocytes and lymphocytes which act as critical components in the immune system to cause the chronic inflammation and lung tissue damage. Obviously, treatment aiming at these inflammation processes may hinder the disease progress potentially.
Triggering receptor expressed on myeloid cell-1 (TREM-1) is a kind of immunoglobulin mainly expressed on the cell membrane of neutrophils, monocytes and macrophages. TREM-1 amplifies toll-like receptor-initiated responses to potentiate the role of pro-inflammatory chemokines and cytokines [2]. Like many membrane bound receptors, TREM-1 also exists in the soluble form (sTREM-1) in human body fluids, which can be tested and measured. Studies reported that sTREM-1 levels can be potentially used for early diagnosis and as a prognosis marker of some infectious diseases. For example, in patients with bacterial pneumonia, sTREM-1 levels in bronchoalveolar lavage fluid were significantly increased [3]. In lipopolysaccharide (LPS)-induced acute lung injury mice, TREM-1 depletion resulted in decreased systematic cytokine production and improved survival [4]. Elevated serum sTREM-1 levels reflected higher severity and poor prognosis in COPD patients [5]. Obviously, TREM-1 is involved in inflammation and interfering with it might ameliorate the inflammation.
Statins are inhibitors of 3-Hydroxymethyl-3-glutaryl Coenzyme A reductase, used clinically as lipid control regime for hyperlipemia especially hypercholesterolemia. In addition to their lipid-lowering property, statins reportedly possess some anti-inflammatory and immunomodulatory effects. In a vitro study, statin reduced the inflammatory cytokine production (IL-6, -8) in air interface Calu-3 cells after LPS stimulation [6]. Clinical studies demonstrated that in patients with inflammatory lung diseases such as asthma, lung injury, and COPD, statins were promising treatment [[7], [8], [9]]. For example, in COPD patients, statins could reduce the pulmonary-related mortality [10]. Meanwhile, other study presented the different conclusions [11]. Indeed, the role and underlying cellular mechanism of statins on inflammatory cells have been poorly explored to date. In this study, we observed whether pravastatin sodium could attenuate TREM-1-mediated inflammation in human PBMCs and if the attenuation works via NF-κB signaling pathway.
Section snippets
Isolation and culture of PBMCs
The protocol of this study was approved by the Ethic Committee of Anhui Provincial Hospital, and an agreement was received by each of the patient. PBMCs were obtained by density gradient centrifugation using the lymphocyte separation solution according to the manufacturer's instruction. Blood samples from stable stage COPD patients were collected in EDTA tubes. Blood was diluted 1:1 with sterile 1XPBS and layered over sterile Lymphoprep™. Samples were centrifuged (550 g, 20 min, 25 °C). The
Cytotoxicity
To determine a non-cytotoxic concentration of the pravastatin sodium, gradient concentrations of pravastatin sodium were tested and cell viability was observed. The results showed that cells survived greater than 90% when treated with pravastatin sodium at a concentration less than 100 μM. Higher doses of pravastatin led to lower viability. Therefore, we chose the concentration of 10, 50, and 100 μM for the subsequent experiments.
Effect of pravastatin sodium on LPS-upregulated TREM-1 expression in PBMCs
Referring to the reported article [12], we detected TREM-1 mRNA
Discussion
COPD is a multi-component disease involving long-term inflammation in the lung. The chronic inflammatory responses were persistent, leading to tissue damage and organ dysfunction. PBMCs could be attracted and recruited by the local inflammatory mediators in the lung tissue and play a critical role in the inflammatory process. In this study, we observed the changes of stimulated PBMCs in vitro, concentrating on the effects of pravastatin sodium on TREM-1-mediated inflammatory responses and the
Conflicts of interest
No conflicts exist for the specified authors.
Acknowledgements
This study was supported by the Natural Science Foundation of Anhui Province, China (1308085MH115) and Science and Technology Foundation of Anhui Province, China (1704f0804007).
References (23)
- et al.
The impact of statin drug use on all-cause mortality in patients with COPD: a population-based cohort study
Chest
(2017) - et al.
Increased serum TREM-1 level is associated with in-stent restenosis, and activation of TREM-1 promotes inflammation, proliferation and migration in vascular smooth muscle cells
Atherosclerosis
(2017) - et al.
Vasoactive intestinal peptide overexpression mediated by lentivirus attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting inflammation
Mol. Immunol.
(2018) - et al.
Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia
J. Am. Coll. Cardiol.
(2000) - et al.
Suppression of NF-κB pathway by crocetin contributes to attenuation of lipopolysaccharide-induced acute lung injury in mice
Eur. J. Pharmacol.
(2012) - et al.
Knockdown of TREM-1 suppresses IL-1beta-induced chondrocyte injury via inhibiting the NF-kappaB pathway
Biochem. Biophys. Res. Commun.
(2017) - et al.
The pathology of chronic obstructive pulmonary disease
- et al.
TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors
J. Leukoc. Biol.
(2012) - et al.
Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis of infectious diseases
Front. Med.
(2017) - et al.
Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients
Arterioscler. Thromb. Vasc. Biol.
(2002)
Soluble triggering receptor expressed on myeloid cells 1 is released in patients with stable chronic obstructive pulmonary disease
Clin. Dev. Immunol.
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The authors contributed equally to this work.