Introduction: Dysregulation of the lipid metabolism has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF);however, the role of free fatty acids (FFA) is not well defined. Aim: to investigate the role of FFA in the pathogenesis in IPF Methods: Fatty acid methyl esters were analyzed with Agilent 7890/5975 Gas Chromatography-Mass Spectrometry and HP-5 MS 30 m * 250 µm * 0.25 µm column (Agilent 19091S-433) in the lung tissues of controls (n=10) and IPF patients (n=10). To evaluate the function of FFA, human lung fibroblasts (MRC-5 cells) were treated with TGF-ß1 (5 ng/ml) and/or FFAs including palmitic acid, stearic acid, oleic acid and linoleic acid. Cell viability and protein expression were measured via MTT assay and western blot analysis, respectively. Results: Although the levels of palmitic acid, oleic acid and linoleic acid were elevated, the level of stearic acid was significantly reduced in the lung tissues of patients. Palmitic acid, oleic acid or linoleic acid significantly enhanced the TGF-ß1 induced expression of α-smooth muscle actin (SMA) and collagen type-1 in MRC-5 cells;however, stearic acid significantly reduced them. Moreover, palmitic acid and linoleic acid increased the TGF-ß1 induced proliferation of MRC-5 cells, but stearic acid decreased it. Stearic acid significantly inhibited the levels of p-Smad2/3 in MRC-5 cells treated with TGF-ß1. Conclusion: Our findings suggest that FFAs may have effects on pulmonary fibrosis by regulating TGF-ß1 induced activation and proliferation of fibroblasts and be implicated as potential therapeutic targets in IPF.
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) has a variable clinical course for which predicting prognosis is difficult. However, the role of blood biomarkers in RA-ILD is ill-defined. The aim of this study was to investigate the prognostic value of Krebs von den Lungen-6 (KL-6) levels in RA-ILD patients. The medical records of 84 patients with RA-ILD were retrospectively reviewed. Plasma KL-6 levels were measured by Nanopia KL-6 assay (SEKISUI MEDICAL, Tokyo), using latex-enhanced immunoturbidimetric assay. The median follow-up period was 61 months. Mean age was 61.4 years, 45.2% were men, 44.0% were ever-smokers, and 35.7% showed a usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography. The median KL-6 level at baseline was 741.2 U/mL (interquartile range, 439.7-1308.9 U/mL). On multivariate logistic regression analysis, a high KL-6 level (≥ 640 U/mL) was an independently associated with a UIP pattern (odds ratio [OR], 5.173; P = 0.005) with old age (OR, 1.104, P = 0.005). On multivariate Cox analysis, a high KL-6 level (≥ 685 U/mL) was an independent prognostic factor for the mortality (hazard ratio [HR], 2.984; P = 0.016) with a older age (HR, 1.061; P = 0.030), male sex (HR, 3.610; P = 0.001), lower forced vital capacity (HR, 0.957; P = 0.002), and a UIP pattern (HR, 4.034; P = 0.002). Our results suggest that high KL-6 levels might be useful as a biomarker for the presence of a UIP pattern and prognosis in patients with RA-ILD.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown aetiology [1] with ageing being one of the major risk factors [2]. Several ageing-related changes, such as the overproduction of mitochondrial reactive oxygen species, low adenosine triphosphate production, reduced mitochondrial biogenesis and inadequate mitochondrial (mt)DNA repair [3] have also been reported in the IPF lungs [4, 5] and in a bleomycin-induced mouse model [6]. Plasma cell-free DNA, including mtDNA, is released from dying cells into the circulatory system in response to injury [7]. Since circulating mtDNA contains CpG-rich sequences similar to bacterial DNA, disengaged mtDNA can activate the innate immune system by functioning as a damage-associated molecular pattern [8] and contribute to the stimulation of the profibrotic pathway [9]. Plasma mtDNA level could serve as a potential marker for disease progression and acute exacerbation in idiopathic pulmonary fibrosis We would like to thank Ye-Jee Kim (Dept of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea) for their advice on statistical analysis.
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