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Introduction
Airway inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, are major causes of morbidity and mortality in patients, and place a substantial burden on healthcare systems (1). Bacterial infection, cigarette smoking and air pollutants are implicated in the onset and progression of lung inflammation (2). Lipopolysaccharides (LPS) is the major outer surface membrane component of Gram-negative bacteria and a biologically active component present in cigarette smoke (3). Thus, LPS-mediated inflammatory response is a major lung inflammation source from exposure to both gram-negative bacterial infection and cigarette smoke. During this inflammatory response, macrophages first help in endocytosis of bacterium debris, followed by generation of inflammatory cytokines and expansion of the local inflammatory response (4,5). In addition, the respiratory epithelium has an active role in the airway defense through the production of cytoprotective mucus and through coordinating local inflammation responses by producing proinflammatory cytokines. These cytokines, however, also result in bronchial maladaptations, including pulmonary dysfunction, increased mucin production and protease-antiprotease imbalance (6–8).
It has been reported that proinflammatory cytokine production is induced by many stimuli through the mitogen-activated protein kinase (MAPK), nuclear factor (NF)-κB or Janus kinase (JAK)/signal transducer and activator of transcription (STAT3) signaling cascades. For instance, LPS-induced MAPK and JAK/STAT3 activation results in activation of the downstream transcriptional factors NF-κB, activator protein (AP)-1, peroxisome proliferator-activated receptor (PPAR) and STAT3, which mediate the transcription and translation of proinflammatory genes (9–11). In the present study, in order to investigate the mechanisms of LPS induced-inflammatory response in airway epithelial and macrophage cells, the effects of LPS exposure on the expression of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, matrix metallopeptidase (MMP)-9 and tissue inhibitor of metalloproteinases (TIMP)-1 were examined in human airway epithelial H292 cells and macrophage THP-1 cells. Subsequently, inflammation-related transcription factors and intracellular signaling pathways that may be involved in LPS-induced pro-inflammation cytokine production were explored.
Materials and methods
Cell culture
H292 human lung mucoepidermoid carcinoma cells and THP-1 human monocytic cells were obtained from the American Type Culture Collection (Manassas, VA, USA). The cells were maintained in RPMI-1640 (Beijing Solarbio Science and Technology Co., Ltd., Beijing, China) supplemented with 10% fetal calf serum (Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA), penicillin (100 U/ml) and streptomycin (100 mg/ml), and incubated...