Normalization of the levels of inflammatory molecules in Mycobacterium smegmatis-infected U937 cells by fibrate pretreatment.

Sung-Jo Kim,Sungweon Ryoo,Hak-Kyo Lee,Minho Hong,Ki Duk Song,Tae-Hwe Heo

doi:10.1186/0717-6287-47-42

Sung-Jo Kim, Sungweon Ryoo + Show 4 more

Open Access

https://doi.org/10.1186/0717-6287-47-42

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Abstract

BackgroundTuberculosis (TB) is a respiratory tract disease caused by Mycobacterium tuberculosis infection. M. tuberculosis exploits immune privilege to grow and divide in pleural macrophages. Fibrates are associated with the immune response and control lipid metabolism through glycolysis with β-oxidation of fatty acids.ResultsIn this study, we investigated the effect of fibrate pretreatment on the immune response during M. smegmatis infection in U937 cells, a human leukemic monocyte lymphoma cell line. The protein expression of tumor necrosis factor α (TNF-α), an inflammatory marker, and myeloid differentiation primary response gene 88 (MyD88), a toll like receptor adaptor molecule, in the infected group increased at 1 and 6 h after M. smegmatis infection of U937 cells. Acetyl coenzyme A acetyl transferase-1 (ACAT-1), peroxisome proliferator-activated receptor-α (PPAR-α), TNF-α, and MyD88 decreased in U937 cells treated with fibrates at 12 and 24 h after treatment. More than a 24 h pretreatment with fibrate resulted in similar expression levels of ACAT-1 and PPAR-α between infected vehicle control and infected groups which were pretreated with fibrate for 24 h. However, upon exposure to M. smegmatis, the cellular expression of the TNF-α and MyD88 in the infected groups pretreated with fibrate for 24 h decreased significantly compared to that in the infected vehicle group.ConclusionThese results suggest that fibrate pretreatment normalized the levels of inflammatory molecules in Mycobacterium smegmatis-infected U937 cells. Further studies are needed to confirm the findings on pathophysiology and immune defense mechanism of U937 by fibrates during M. tuberculosis infection.

Highlights

Tuberculosis (TB) is a respiratory tract disease caused by Mycobacterium tuberculosis infection
Identification of M. smegmatis infection The U937 cells differentiated by Phorbol myristate acetate (PMA) were exposed to M. smegmatis to identify the infection
After lysis of differentiated U937 cells, the collected genomic DNA was used with a specific primer designed for mannose-6-phosphate isomerase class I (ManA) and methionine amino peptidase (MetAP), which are both expressed in M. smegmatis

Summary

Introduction

Tuberculosis (TB) is a respiratory tract disease caused by Mycobacterium tuberculosis infection. M. tuberculosis exploits immune privilege to grow and divide in pleural macrophages. Mycobacterium tuberculosis causes tuberculosis (TB) infection, a disease which kills two million people every year [1,2,3]. Phagocytosis of M. tuberculosis by alveolar macrophages results in the accumulation of oxidized low-density lipoproteins which provides immune privilege to the pathogen. Several fibrates have been developed, including bezafibrate, fenofibrate, and gemfibrozil. Fenofibrate and gemfibrozil have been used in North America and bezafibrate and ciprofibrate in Europe. It was reported that gemfibrozil, a commonly prescribed hypolipidemic drug, blocked TB growth by inhibiting enoyl reductase [20] and bezafibrate differentiates human myeloid leukemia cells [21]

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