Adipose tissue develops lipids, aberrant adipokines, chemokines, and pro-inflammatory cytokines as a consequence of the low-grade systemic inflammation that characterizes obesity. This low-grade systemic inflammation can lead to insulin resistance (IR) and metabolic complications, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Although the CXC chemokines consists of numerous regulators of inflammation, cellular function, and cellular migration, it is still unknown that how CXC chemokines and chemokine receptors contribute to the development of metabolic diseases (such as T2D and NAFLD) during obesity. In light of recent research, the objective of this review is to provide an update on the linkage between the CXC chemokine, obesity, and obesity-related metabolic diseases (T2D and NAFLD). We explore the differential migratory and immunomodulatory potential of CXC chemokines and their mechanisms of action to better understand their role in clinical and laboratory contexts. Besides that, because CXC chemokine profiling is strongly linked to leukocyte recruitment, macrophage recruitment, and immunomodulatory potential, we hypothesize that it could be used to predict the therapeutic potential for obesity and obesity-related diseases (T2D and NAFLD).

A crucial component of the immune system are chemokiness. Chemokine\'s dysregulation has been linked to a number of pathological diseases. Recently, CXCL17, a chemokine belonging to the CXC subfamily, was identified. With regard to a number of physiological conditions and disorders, CXCL17 either has homeostatic or pathogenic effects. Some research suggests that CXCL17 is an orphan ligand, despite the fact that G protein-coupled receptor (GPR) 35 has been suggested as a possible receptor for CXCL17. Since CXCL17 is primarily secreted by mucosal epithelia, such as those in the digestive and respiratory tracts, under physiological circumstances, this chemokine is referred to as a mucosal chemokine. Macrophages and monocytes are the cells that express GPR35 and hence react to CXCL17. In homeostatic conditions, this chemokine has anti-inflammatory, antibacterial, and chemotactic properties. CXCL17 promotes angiogenesis, metastasis, and cell proliferation in pathologic circumstances like malignancies. However, other studies suggest that CXCL17 may have anti-tumor properties. Additionally, studies have shown that CXCL17 may have a role in conditions such as idiopathic pulmonary fibrosis, multiple sclerosis, asthma, and systemic sclerosis. Additionally, deregulation of CXCL17 in some diseases may serve as a biomarker for diagnosis and prognosis. Clarifying the underlying mechanism of CXCL17\'s activity in homeostatic and pathological situations may thus increase our understanding of its role and hold promise for the development of novel treatment strategies.

Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors-CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8. First, we present basic information on the effect of these chemoattractant cytokines on cancer processes. We then discuss the effect of hypoxia-induced changes on CXC chemokine expression on the angiogenesis, lymphangiogenesis and recruitment of various cells to the tumor niche, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), regulatory T cells (Tregs) and tumor-infiltrating lymphocytes (TILs). Finally, the review summarizes data on the use of drugs targeting the CXC chemokine system in cancer therapies.

This review highlights a selection of recently published literature in the area of osteoarthritis biology. Major themes transpiring from a PubMed search covering the year between the 2014 and the 2015 Osteoarthritis Research Society International (OARSI) World Congress are explored. Inflammation emerged as a significant theme, revealing complex pathways that drive dramatic changes in cartilage homeostasis and in the synovium. Highlights include a homeostatic role for CXC chemokines in cartilage, identification of the zinc-ZIP8-MTF1 axis as an essential regulator of cartilage catabolism, and the discovery that a small aggrecan fragment can have catabolic and pro-inflammatory effects through Toll-like receptor 2. Synovitis can promote joint damage, partly through alarmins such as S100A8. Synovitis and synovial expression of the pro-algesic neurotrophin, Nerve Growth Factor, are associated with pain. Increasingly, researchers are considering specific pathogenic pathways that may operate in distinct subsets of osteoarthritis associated with distinct risk factors, including obesity, age, and joint injury. In obesity, the contribution of metabolic factors and diet is under intense investigation. The role of autophagy and oxidative stress in age-related osteoarthritis has been further explored. This approach may open avenues for targeted treatment of distinct phenotypes of osteoarthritis. Finally, a small selection of novel analgesic targets in the periphery is briefly discussed, including calcitonin gene-related peptide and the neuronal sodium voltage-gated channels, Nav1.7 and Nav1.8.

Stromal cell derived factor (SDF), expressing on bone marrow stromal cells is a CXC-type chemokine, which specifically chemoattracts hematopoietic stem cells (HSCs) expressing CXCR4. SDF plays important roles in homing and mobilizing of HSCs. In this paper the regulatory mechanism of SDF/CXCR4 in the HSC migration process is mainly reviewed.

The complete genetic content of human cytomegalovirus (HCMV) has been difficult to determine, since most strains studied in the laboratory have been extensively passaged in human fibroblast cultures which can change the genetic content as well as the biological properties of the virus. Approximately 13 kb of novel DNA sequences located near the right edge of the unique long (UL) component of the genome has been discovered in Toledo, clinical isolates and certain stocks of Towne. This region of novel sequence, designated the UL/b\' region, encodes several interesting proteins including vCXC-1, a potent IL-8 homologue, and UL144, a member of the TNF receptor family. This region is missing from the prototypic laboratory variants of Towne and AD169. In contrast to Toledo and other low passage isolates which have relatively small repeats bracketing the UL component, the Towne and AD169 laboratory variants contain large (>10 kb) b/b\' repeats. The large size of these repeats in AD169 and Towne appear to have arisen as compensation for the loss of sequences from the UL/b\' region that existed in less passaged variants of these strains. Consequently, many of the haploid genes at the left edge of the prototypic wild-type (wt) UL component are diploid in AD169 and Towne. We hypothesise that this plasticity of the genome at the right edge of the UL component results from extensive passage and adaptation to replication in fibroblasts in vitro. Further work will be required to understand the complete genetic content of wt HCMV.

Knowledge of chemokine receptor expression by human syncytiotrophoblast has important implications for our understanding of maternal-fetal HIV transmission as well as for understanding the regulation of placental growth and development. This review discusses what is known about chemokine receptor expression by trophoblast and other placental cells. In addition, new data are presented showing that CXCR4 is expressed on the syncytiotrophoblast surface. In other new studies, leukocyte-mediated HIV-1Lai(an X4 strain) infection of syncytiotrophoblast cultures was reduced when stromal derived factor-1alpha was added to the cocultures, consistent with a role for CXCR4. The available information on chemokine receptor expression by trophoblast is discussed in terms of the apparent selective transmission of R5 strains. Studies in other systems indicate that caution must be used in predicting chemokine receptor usage by different HIV isolates, particularly when the route of infection is cellmediated.

The intestinal epithelium plays an important role in the recognition of pathogenic organisms and in the recruitment of inflammatory cells to the mucosa. Epithelial chemokine production may constitute a key target in future therapies for inflammatory bowel disease (IBD). Chemokines are divided into two subfamilies, the C-C family and C-X-C family. Most C-C chemokines target mononuclear cells and many C-X-C chemokines attract neutrophils. Interleukin-8 (IL-8), a C-X-C chemokine, acts as a motor for the recruitment of neutrophils into the non-inflamed mucosa and is present in both enterocytes and mucosal inflammatory cells. Epithelial cells may be the first to signal the presence of pathogens, as well as contributing to IL-8 production in IBD. Data have also shown that intestinal epithelial cells are able to respond to IL-1 and tumour necrosis factor-alpha (TNF-alpha) at concentrations known to occur in the inflamed mucosa. Monocyte chemotactic protein-1 (MCP-1), a member of the C-C chemokine family, is noticeably increased in IBD. These data show that C-X-C and C-C chemokines are equally important properties of mucosal epithelial cells. The effects of two anti-inflammatory drugs (dexamethasone and cyclosporin) on chemokine production are significantly different and this provides a rationale for combination therapy.