We also measured macrophage infiltration and CLS

We also measured macrophage infiltration and CLS presence in peri-gonadal AT from db/db mice and controls. CLS are morphological features within AT that are accurate indicators of adipocyte death and macrophage infiltration [56]. An earlier study showed that CLS macrophages account for >90% of the total adipose tissue macrophages in diabetic and insulin resistant mice and they display a pro-inflammatory phenotype [57]. Therefore, Mac-2+ CLS can be used as a surrogate for both adipocyte death and pro-inflammatory macrophage infiltration in adipose tissue. Recently, our group reported that 12LO protein in AT of diet-induced obese and insulin resistant mice is predominantly localized in CLS [58]. Moreover, both 12LO expression and the number of Mac-2 positive CLS are reduced in mice treated with the DPP4 inhibitor sitagliptin in parallel with improvement of insulin sensitivity and glucose tolerance [58]. In this paper we show an age-dependent dramatic increase in Mac-2+ CLS in perigonadal fat in db/db mice but not in heterozygous controls which is mirrored by an increase in 12-(S) HETE and 15(S)-HETE production in the same tissues. Therefore, a reduction in Mac-2+ CLS can be used as a marker to monitor anti-inflammatory effects of selective 12-LO inhibition in AT.
Author’s contributions
Acknowledgments
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 Rizatriptan Benzoate sale [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].