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  • Activated MAP kinases transform the stimulus into the pathop


    Activated MAP kinases transform the stimulus into the pathophysiological responses by phosphorylating downstream substrates, including transcription factors, cytoskeletal proteins involved in mRNA translation (Li et al., 2015). Among the numerous effectors that intervene in the TNF-α action is an activator protein (AP-1), which comprises transcription factors belonging to the jun and fos families (Adiseshaiah et al., 2006). In response to stress and cytokine, JNK1/2 and p38 kinases bind to transcription factors that regulate c-Jun (Tsou et al., 2012). We showed that there is an increase in phosphorylation of c-Jun expression in TNF-α stimulated RA-FLS and the pretreatment of TQ is able to reduced TNF-α induced expression of p-c-Jun. The following is the supplementary data related to this article.
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    Conflict of interest
    Acknowledgments This study was supported by the NIH grant AR063104 (S.A.), the Arthritis Foundation Innovative Research Grant (S.A.), the start-up funds from Washington State University (S.A.), and the ASPET summer undergraduate research fellowship (SURF) award (O.H.). Authors also thank the National Disease Research Interchange (NDRI), Philadelphia and Co-operative Human Tissue Network (CHTN) for providing the synovial tissue for research.
    Introduction Fine particulate matter (PM2.5; aerodynamic diameter <2.5 μm) is a well-known air pollutant threatening public health. Long-term exposure to PM2.5 has been associated with reduction in pulmonary function, exacerbation of chronic respiratory diseases such as Penciclovir Sodium mg and chronic obstructive pulmonary disease (COPD), and increased incidence and mortality of lung cancer (Wu et al., 2014; Karakatsani et al., 2012; Raaschou-Nielsen et al., 2013). Epidemiological studies have revealed an inverse correlation between PM2.5 inhalation and average life span (Xing et al., 2016). Experimental evidence has indicated that administration of PM2.5 to animals by intratracheal instillation induces lung inflammation, hyperemia, pulmonary oxidative stress, lung vascular hyperpermeability, alveolar epithelial dysfunction and lung injury (Li et al., 2015a, Li et al., 2015b; Wang et al., 2015). The toxicity of PM2.5 is mainly due to the small size of the particle that allows PM2.5 to bypass human innate defense mechanism and go deeply into the bronchial to deposit in the alveolar, and the adsorbed toxic substances including endotoxin, polycyclic aromatic hydrocarbons (PAHs), sulfate and heavy metals (Falcon-Rodriguez et al., 2016). The research regarding the distribution of chemical species in PM2.5 and PM10 demonstrated that SO42−, NH4+, organic carbon (OC) and elemental carbon (EC) mainly existed in PM2.5, while crustal species were the most abundant components in PM10, indicating a crucial role of PM2.5 in poor air quality (Zhou et al., 2016). Since the environmental problem cannot be solved immediately, it is urgent to identify novel preventive and therapeutic strategies to protect human respiratory system. Hyaluronan (HA) is a major component of extracellular matrix (ECM) with important roles in physiological and pathological processes in almost all tissues. High molecular weight HA (HMW-HA; >500 kDa) exists predominantly in healthy tissue, suppressing inflammatory cytokine production, neutrophil-endothelial cell adhesion, tumor progression and macrophage phagocytosis by interaction with HA binding proteins such as CD44, RHAMM, SHAP and LYVE1 (Hussain et al., 2016; Tian et al., 2013; He et al., 2013; Alam et al., 2005; Ruppert et al., 2014). Besides, the anti-apoptotic and anti-oxidative role of HMW-HA has been revealed in multiple cellular models, including UV-induced epithelial corneal cell apoptosis and IL-17A-mediated nasal epithelial cell inflammation (Albano et al., 2016; Pauloin et al., 2009). For patients with osteoarthritis (OA), intra-articular injection of HMW-HA is an effective and safe treatment to relieve pain and prevent cartilage degradation (Hashizume and Mihara, 2010). Animal studies demonstrated that HMW-HA improved measures of surface activity, lung compliance, gas exchange and pulmonary mechanics in meconium-treated rats, and ameliorated pulmonary inflammation, lung edema, airway epithelial cell apoptosis and airway mucous plugging in rats exposed to smoke (Lu et al., 2005; Huang et al., 2010).