Proteomic profiling change during the early development of silicosis disease

Abstract

Background: Silicosis is one of several severe occupational diseases for which effective diagnostic tools during early development are currently unavailable. In this study we focused on proteomic profiling during the early stages of silicosis to investigate the pathophysiology and identify the proteins involved.Methods: Two-dimensional (2D) gel electrophoresis and MALDI-TOF-MS were used to assess the proteomic differences between healthy individuals (HI), dust-exposed workers without silicosis (DEW) and silicosis patients (SP). Proteins abundances that differed by a factor of two-fold or greater were subjected to more detailed analysis, and enzyme linked to immunosorbent assay (ELISA) was employed to correlate with protein expression data.Results: Compared with HI, 42 proteins were more abundant and 8 were less abundant in DEW, and these were also differentially accumulated in SP. Closer inspection revealed that serine protease granzyme A, alpha-1-B-glycoprotein (A1BG) and the T4 surface glycoprotein precursor (TSGP) were among the up-regulated proteins in DEW and SP. Significant changes in serine proteases, glycoproteins and protooncogenes may be associated with the response to cytotoxicity and infectious pathogens by activation of T cells, positive regulation of extracellular matrix structural constituents and immune response, and fibroblast proliferation. Up-regulation of cytokines included TNFs, interferon beta precursor, interleukin 6, atypical chemokine receptor 2, TNFR13BV, and mutant IL-17F may be involved in the increased and persistent immune response and fibrosis that occurred during silicosis development.Conclusions: Granzymes, glycoproteins, cytokines and immune factors were dramatically involved in the immune response, metabolism, signal regulation and fibrosis during the early development of silicosis.Proteomic profiling has expanded our understanding of the pathogenesis of silicosis, and identified a number of targets that may be potential biomarkers for early diagnosis of this debilitating disease. J Thorac Dis 2016;8(3):329-341 jtd.amegroups.com extracellular apoptosis related factor (ECM), cytokines and lipid-associated proteins were all reportedly involved in the development of silicosis (3,4). Unfortunately, an effective method involving biomarkers for early diagnosis remained unavailable at present.Significant cellular and molecular alterations ensued following inhalation and deposition of silica minerals in lung tissues (5). Lower-level exposure to silica particles triggered reversible inflammatory lesions, whereas highlevel exposure led to long-term effects on inflammation, cell proliferation, deposition of collagen and extracellular matrix components in mesenchymal cells (1). Alveolar macrophages (AM), neutrophils, T-lymphocytes and mast cells were all involved in fibrogenesis, and cross-talk between these cells played an important role in disease progression. In studies on the interaction of mast cells and neutrophils in mice, animals with intact mast cells endured more severe lung lesi...

CircHECTD1 mediates pulmonary fibroblast activation via HECTD1

“…Numerous studies have shown that pulmonary fibrosis is mainly caused by the activation of macrophages, which release inflammatory factors and cytokines to influence the activation and migration of downstream effector cells. 1,4,5,31 However, the direct effects of SiO 2 on protein production and functional changes in pulmonary fibroblasts have not been studied extensively. The current study focused mainly on functional changes in fibroblasts in the fibrosis stage, which suggests that the direct effect of SiO 2 on fibroblasts may play an important role in the pathogenesis of silicosis (Figure 8).…”

“…Once diagnosed, it is already in the late stage of irreversible fibrosis, and effective treatment for pulmonary fibrosis in the late stage is lacking. 4 The pathophysiology of silicosis starts with phagocytosis of silica in macrophages, which causes an inflammatory cascade that leads to excessive fibroblast proliferation and migration, and gradually forms fibrosis. 5,6 Despite numerous studies that have been conducted to explore the toxicity of crystalline silica, the specific mechanism underlying silicosis is not well understood.…”

Emerging Role of Immunosuppression in Diseases Induced by Micro- and Nano-Particles: Time to Revisit the Exclusive Inflammatory Scenario

“…Inflammatory cell accumulation, collagen deposition, or malignant mesothelioma in silica- or asbestos-treated mice was markedly decreased by suppressing genetically or pharmacologically these key inflammatory mediators ( 13 , 29 ). Increased levels of TNF-α, IL-1, IFN-γ, and IL-17 have been observed in human under conditions of developing silicosis, asbestosis or mesothelioma ( 30 – 33 ). These findings convincingly indicate a causal relationship between excessive or maintained accumulation of pro-inflammatory cells and cytokines and the establishment of particle-induced chronic diseases.…”

Serum concentrations of Krebs von den Lungen-6, surfactant protein D, and matrix metalloproteinase-2 as diagnostic biomarkers in patients with asbestosis and silicosis: a case–control study

“…Several biomarkers, such as interleukin-1β, type IV collagen, tumor necrosis factor-α, neopterin, and proteomic profiling, have shown potential significance in patients with lung fibrosis [ 18 – 21 ]. However, no previous investigations have evaluated the diagnostic values of pneumocyte-derived biomarkers in various pneumoconioses.…”