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  • In the present study we showed


    In the present study, we showed that 15-LOX metabolites, which are the precursors of anti-inflammatory and pro-resolving lipid mediators, were decreased in the unaffected skin area of the OS model rats by comprehensive lipidomics analyses. Furthermore, subsequent microarray analyses demonstrated that some pro-inflammatory chemokines/cytokines were elevated. From these results, we speculate that the pro-inflammatory state plays a role in triggering the pathogenesis of OS syndrome (Fig. 6). Our findings may provide insights into the future development of OS therapy, such as using 15-LOX metabolites or their derivatives.
    Conflicts of interest
    Acknowledgements We thank Ichiro Hikita for useful discussions. This research was supported by the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program, Ministry of Education, Culture, Sports, Science and Technology, Japan, and by a grant from Shionogi & Co., Ltd, Japan.
    Introduction Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis and pneumonia in infants and young children [1]. It's so common that nearly all children have been infected with the virus during the first year of life [2]. In addition, adults become re-infected despite the presence of KN-92 phosphate [3]. During RSV infection, lung epithelium and alveolar macrophages are the first cells that are infected [4]. It was shown that early inflammatory and immune responses of the host may be crucial in response to RSV infection [5]. RSV bronchiolitis is associated with development of a wide range of pro-inflammatory cytokines and chemokines and an extensive inflammatory infiltration in the lower airways, comprising neutrophils monocytes, T cells and eosinophils [6]. RSV infection has been shown to induce Chemokine (C-C motif) ligand 5 (CCL5) and Chemokine (C-C motif) ligand 3(CC L3) activity in-vivo and in-vitro which are present in inflammatory infiltrates or in respiratory secretions of RSV-infected children [7]. However, the exact mechanisms of RSV-induced airway disease, controlling the influx of specific inflammatory cells and its long-term consequences such as recurrent wheezing in later life are not well understood [5], [6]. Eukaryotic cells respond to a large number of distinct extracellular signals and environmental stresses, and the responses usually involve signal transduction pathways that lead to the activation of specific sets of genes. Thus, to define the innate host response to the infection, considerable effort has been focused on the transcriptional activation of cellular genes by viruses [8]. Besides cytokines and chemokines, lipid mediators are critically involved in the development of pulmonary inflammation and play important roles in the pathophysiology of allergen-induced inflammation and lung remodeling in asthma [9]. Lipoxygenases (LOX) are a family of enzymes capable of incorporating oxygen into unsaturated fatty acids [9]. The 15(S)-lipoxygenase (15-LOX) pathway has several roles in the pathogenesis of inflammatory lung disorders and may thus constitutes a potential drug target [10]. 15-LOX plays a janus role in inflammation with pro-inflammatory and anti-inflammatory effects on cell cultures and primary cells and even opposite effects on atherosclerosis in two different animal species [11]. A high homology exists between 12/15-LOX in mice and 15-LOX in humans. Thus, the murine 12/15-LOX is considered as the mouse ortholog of human 15-LOX [9]. Murine 12/15-LOX and human 15-LOX have 74% identity in primary structure, and both are dual-specificity lipoxygenases [12]. 12/15-LOX is expressed in a variety of tissues, with the highest expression levels in monocytes and macrophages [9]. A variety of vascular cells are able to express 12/15-LOX, including endothelial cells, smooth muscle cells, and immune cells [12].
    Material and methods
    Discussion RSV is a major cause of lower respiratory tract infections in infancy and early childhood. Several observations suggest that immunological mechanisms may be the key to understand the severity of RSV bronchiolitis in infancy. Several laboratories have demonstrated that RSV induced cytokines such as TNF-alpha and IL8 and chemokines such as CCL5 and CCL3 release from immune and epithelial cells of the human lower respiratory tract and play a fundamental role in the pathogenesis of RSV-induced disease [7], [15].