CXC Receptor Expression Research Articles

Role of CXC group chemokines in lung cancer development and progression.

Clinical and translational research on lung cancer patients undergoing surgical treatment can provide valuable scientific data and unique opportunity to study tumor microenvironment. CXC chemokines, which are members of a big family of cytokines, are undoubtedly involved in tumor growth regulation and metastasizing pathways. For better understanding of CXC chemokine involvement in the process of carcinogenesis we have studied the cohort of early stage non-small cell lung cancer patients undergoing surgery with curative intent. Our aim was to assess CXC chemokine ligand (CXCL) levels in patient blood samples representing systemic circulation and tumor microenvironment; assess CXC chemokine receptor (CXCR) expression in tumor tissue; and measure tumor infiltrating immune cell subpopulations. A total of 54 patients with NSCLC had radical lung resection were enrolled in a single center prospective study and were followed-up annually for up to six years. During surgical procedure peripheral and tumor draining blood samples were taken. CXCL1, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11 and CXCL12 levels were determined by ELISA, and chemokine concentration gradient was calculated. Tumor infiltrating immune cells (T helper cells, T cytotoxic cells, macrophages, B cells, plasma cells) and expression of CXCR1, CXCR2, CXCR3 and CXCR4 in tumor tissue were assessed by immunohistochemistry. Statistically significant decrease in chemokine concentration was found for CXCL4 (P=0.002) and CXCL5 (P=0.011), and statistically significant concentration increase was found for CXCL7 (P=0.001) in total cohort. We have found statistically significant CXC chemokine concentration change for majority of chemokines-CXCL1 (P=0.002), CXCL4 (P=0.001), CXCL5 (P=0.013), CXCL7 (P=0.036), CXCL8 (P=0.026), CXCL9 (P=0.034) and CXCL10 (P=0.032) in a group of patients who had good clinical result after surgery with no evidence of relapse, on the other hand patients with cancer recurrence including local and systemic cancer spread did not show any change of chemokine concentration in blood except for CXCL1 (P=0.041). We have also found that chemokine levels and gradients correlate with CXC receptor expression and number of tumor infiltrating immune cell subpopulations. Assessment of tumor microcirculation is useful for evaluation of different types of circulating biomarkers and application of our method can be very wide, integrating thoracic surgeons into translational cancer research.

The Role of CD4+ T Follicular Helper Cells in HIV Infection: From the Germinal Center to the Periphery.

T follicular helper cells (TFh) are key components of the adaptive immune system; they are primarily found in germinal centers (GCs) where their interaction with B cells supports humoral immune responses and efficient antibody production. They are defined by the expression of CXC receptor 5, program death-1, ICOS, and secretion of IL-21. Their differentiation is regulated by B-cell lymphoma 6. The relationship and function of circulating TFh to bona fide TFh resident in the GC is much debated. HIV infection impacts the TFh response with evidence of aberrant TFh function observed in acute and chronic infection. Effective TFh responses are associated with the development of broadly neutralizing antibody responses to HIV and may be important for viral control. In addition, TFh are preferentially infected and act as a key reservoir for latent HIV infection. This review explores recent developments in our understanding of TFh differentiation, regulation, function, and the relationship between cTFh and those in GCs, and the complex interaction between TFh and HIV infection.

Expression of CXC receptor 1 and 2 in esophageal mucosa of patients with reflux esophagitis

Interleukin 8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about the two distinct receptors, CXC receptor (CXCR)-1 and -2. The purpose of this study was to determine CXCR-1 and -2 messenger RNA expression levels in RE. We studied 26 patients with RE and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of CXCR-1 and -2 mRNA levels by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), and another was formalin-fixed for histopathological evaluation. We also examined the association of the expression levels of CXCR-1 and -2 mRNA with histopathological hallmarks of RE. The relative CXCR-1 and -2 mRNA expression levels were rather decreased in esophageal mucosa of patients with RE, compared to those in normal esophagus of controls. There were no significant difference in the relative mRNA expression levels of CXCR-1 and -2 among endoscopic grades of RE based on the Los Angeles classification. Each histopathological hallmark of GERD was not associated with the expression levels of CXCR-1 and -2 mRNA. Apart from overexpression of IL-8, the relative expression levels of CXCR-1 and -2 mRNA were rather lower than expected in the affected esophageal mucosa of patients with RE.

P38 mitogen activated protein kinase is involved in the downregulation of granulocyte CXC chemokine receptors 1 and 2 during human endotoxemia.

Chemokine receptors CXC receptor (CXCR) 1 and 2, and their ligands interleukin (IL)-8 and growth-related oncogene alpha (GRO alpha), are principal regulators of neutrophil activation and migration. To investigate the role of p38 mitogen activated protein kinase (MAPK) in the regulation of CXCR expression during an inflammatory response in vivo, 24 healthy volunteers received an intravenous injection with lipopolysaccharide (LPS) preceded (-3 hr) by a specific p38 MAPK inhibitor (BIRB 796 BS) at a high dose (600 mg) or a low dose (50 mg) or a placebo. The LPS-induced reduction of neutrophil CXCR 1 and 2 expression, as determined by fluorescence-activated cell sorter analysis, was inhibited in volunteers receiving the high dose of the p38 MAPK inhibitor. The kinase inhibitor also dose dependently diminished the LPS-induced rises in plasma IL-8 and GRO alpha levels. These results indicate a principal role for p38 MAPK in regulating factors essential for neutrophil activation and chemotaxis in vivo.