Regulated Upon Activation Normal T Cell Expressed And Secreted Research Articles

The differences of eosinophil- and neutrophil-related inflammation in elderly allergic and non-allergic chronic obstructive pulmonary disease

Background. Chronic obstructive pulmonary disease (COPD) is a common disease in the elderly population and is characterized by airway inflammation. Whether it is a progressive condition resulting from allergic inflammation or a distinct condition involving a pathogen-induced reaction remains unclear. Objectives. To determine the role of allergic inflammation in the pathogenesis of elderly COPD. Methods. A total of 63 elderly adults (21 mite-allergic COPD patients, 29 non-allergic COPD patients, and 13 normal controls) were recruited in this study. The serum-specific IgE for mites, level of interleukin-5 (IL-5), IL-8, leptin, adiponectin, regulated upon activation normal T cell expressed and secreted (RANTES), growth-related oncogene-α (GRO-α), vitamin E, and glutathione (GSH) were determined. Results. The serum levels of GRO-α in patients with COPD were higher in comparison to normal controls (105.8 ± 32.7 vs. 7.5 ± 7.5 pg/mL, p= .021). Compared to patients with non-allergic COPD, patients with mite allergies had a higher serum level of IL-8 (63.2 ± 12.6 vs. 35.0 ± 8.2 pg/mL, p= .022). Although both IL-5 and RANTES levels were increased in COPD patients, there were no significant differences between allergic and non-allergic COPD. There were also no differences in serum levels of leptin, adiponectin, vitamin E, and GSH between COPD patients and normal controls. Conclusions. The increased serum levels of GRO-α indicate that it may have potential as a candidate biomarker for elderly COPD patients. There was no difference of eosinophils-related chemokines in allergic and non-allergic COPD. These results indicated that both adipokines and eosinophil-related chemokines only play trivial roles in the pathogenesis of COPD.

Fluoxetine treatment for major depression decreases the plasma levels of cytokines

Elevated levels of pro-inflammatory biomarkers have been reported in major depressive disorder (MDD). The aim of this study is to investigate the plasma levels of interleukin-18 (IL-18), macrophageinflammatory protein-1α (MIP-1α), monocyte chemoattractant protein 1 (MCP-1), stromal cell derived factor-1 (SDF-1), and regulated upon activation, normal T cell expressed and secreted (RANTES) in patients with MDD before and after eight week treatment of fluoxetine hydrochloride in comparison with normal controls. All subjects were assessed before and after treatment with the Hamilton Depression Rating Scale (HDRS). Our results showed that the symptoms of forty healthy controls and thirty-four patients with MDD were correlated with their plasma levels of IL-18, MIP-1α, MCP-1, SDF-1α, and RANTES. The levels of all five cytokine of patients with MDD were significantly decreased after treatment. However, the levels remained significantly higher than those of the healthy controls (p<0.001). In the seven depressed subjects whose HDRS score fell to below seven after antidepressant therapy comparing with those subjects whose HDRS score larger than seven, the mean levels of IL-18 (p=0.01) and SDF-1α(p<0.05) were significantly lower. Conversely, higher levels of cytokines correlated with a persistently increased severity of symptoms, as measured by the HDRS scores. In conclusion, these findings suggest that MDD is associated with activation of the immune system, and the antidepressant effect of fluoxetine may be mediated in part through its anti-inflammatory effects. Key words : Fluoxetine hydrochloride, major depression, cytokine, chemokine, inflammation.

Flexible use of CCR5 in the absence of CXCR4 use explains the immune deficiency in HIV-1 infected children

CCR5-using HIV-1 (R5 viruses) are usually isolated during acute infection from both adults and children. We have recently demonstrated that R5 viruses with a flexible use of CCR5 (called R5broad) can be detected in children close to birth and are predictive of a fast immunological failure. The aim of the present work was to investigate viral phenotype variation during disease progression in HIV-1 infected children, six slow and eight fast progressors. A total of 74 viral isolates obtained sequentially from 14 HIV-1 infected children were tested for their ability to infect U87.CD4 cells expressing a set of six different CCR5/CXCR4 chimeric receptors or wild-type coreceptors. The sensitivity of 35 R5 viruses to inhibition with the CC-chemokine RANTES (regulated upon activation, normal T-cell expressed and secreted) was evaluated in a peripheral blood mononuclear cells based assay. Viral evolution to R5broad or to R5X4 phenotype occurred with one exception, in all children, although at a different time point according to rate of disease progression. Immune deficiency in the children was significantly associated with the appearance of R5broad phenotype or R5X4 viruses. Analysis of the sensitivity to inhibition by RANTES revealed a significant correlation between the R5broad phenotype and an augmented resistance to this CC-chemokine. We demonstrate that the viral evolution to a more flexible CCR5-use is sufficient to explain the immunological failure in the absence of CXCR4 usage. These results warrant detailed analysis of the R5 phenotype in forthcoming clinical studies introducing CCR5 inhibitors for the treatment of pediatric HIV-1 infection.

In Renal Transplants With Delayed Graft Function Chemokines and Chemokine Receptor Expression Predict Long-Term Allograft Function

Chronic loss of renal allograft function is associated with interstitial fibrosis and tubular atrophy (IF/TA). Independent of the underlying reason, one initial step in the development of fibrosis is chemokine-driven invasion of leukocytes from the blood vessels into the allograft. We studied the role of chemokines in kidney allografts with delayed graft function and the subsequent long-term outcome of renal function and fibrosis. We examined repetitive biopsies of 30 patients without signs of acute rejection but with initially delayed graft function for IF/TA. In addition, we examined the expression of chemokine receptor (CCR)-1 and CCR2 on invaded leukocytes and macrophages and the corresponding ligands regulated upon activation, normal t-cell expressed, and secreted (RANTES) and monocyte chemotactic protein-1 on residential kidney cells. The initial expression of CCR1 positive invading cells and RANTES in glomerular cells correlated with the allograft function 12 months after transplantation and at last follow-up. The expression was independent of donor characteristics such as age, gender, infectious state, cause of death, or use of vasopressive agents. Furthermore, it did not correlate with the duration of cold ischemia time. Among the patients with the most progressive loss of allograft function follow-up biopsy specimen did not reveal any signs of rejection but showed increased CCR1 and RANTES expression in the interstitium suggesting ongoing inflammation and fibrosis. An early expression of RANTES in renal allografts with delayed graft function with consecutive invasion of CCR1 positive cells seems to promote ongoing IF/TA and to worse renal allograft outcome.

T-cell recruitment and Th1 polarization in adipose tissue during diet-induced obesity in C57BL/6 mice.

The role of adaptive immunity in obesity-associated adipose tissue (AT) inflammation and insulin resistance (IR) is controversial. We employed flow cytometry and quantitative PCR to assess T-cell recruitment and activation in epididymal AT (eAT) of C57BL/6 mice during 4-22 weeks of a high-fat diet (HFD (60% energy)). By week 6, eAT mass and stromal vascular cell (SVC) number increased threefold in mice fed HFD, coincident with onset of IR. We observed no increase in the proportion of CD3(+) SVCs or in gene expression of CD3, interferon-γ (IFN-γ), or regulated upon activation, normal T-cell expressed and secreted (RANTES) during the first 16 weeks of HFD. In contrast, CD11c(+) macrophages (MΦ) were enriched sixfold by week 8 (P < 0.01). SVC enrichment for T cells (predominantly CD4(+) and CD8(+)) and elevated IFN-γ and RANTES gene expression were detected by 20-22 weeks of HFD (P < 0.01), coincident with the resolution of eAT remodeling. HFD-induced T-cell priming earlier in the obesity time course is suggested by (i) elevated (fivefold) interleukin-12 (IL-12)p40 gene expression in eAT by week 12 (P ≤ 0.01) and (ii) greater IFN-γ secretion from phorbol myristate acetate (PMA)/ionophore-stimulated eAT explants at week 6 (onefold, P = 0.08) and week 12 (fivefold, P < 0.001). In conclusion, T-cell enrichment and IFN-γ gene induction occur subsequent to AT macrophage (ATMΦ) recruitment, onset of IR and resolution of eAT remodeling. However, enhanced priming for IFN-γ production suggests the contribution of CD4(+) and/or CD8(+) effectors to cell-mediated immune responses promoting HFD-induced AT inflammation and IR.

Urine Peptidomic and Targeted Plasma Protein Analyses in the Diagnosis and Monitoring of Systemic Juvenile Idiopathic Arthritis

PurposeSystemic juvenile idiopathic arthritis is a chronic pediatric disease. The initial clinical presentation can mimic other pediatric inflammatory conditions, which often leads to significant delays in diagnosis and appropriate therapy. SJIA biomarker development is an unmet diagnostic/prognostic need to prevent disease complications.Experimental DesignWe profiled the urine peptidome to analyze a set of 102 urine samples, from patients with SJIA, Kawasaki disease (KD), febrile illnesses (FI), and healthy controls. A set of 91 plasma samples, from SJIA flare and quiescent patients, were profiled using a customized antibody array against 43 proteins known to be involved in inflammatory and protein catabolic processes.ResultsWe identified a 17-urine-peptide biomarker panel that could effectively discriminate SJIA patients at active, quiescent, and remission disease states, and patients with active SJIA from confounding conditions including KD and FI. Targeted sequencing of these peptides revealed that they fall into several tight clusters from seven different proteins, suggesting disease-specific proteolytic activities. The antibody array plasma profiling identified an SJIA plasma flare signature consisting of tissue inhibitor of metalloproteinase-1 (TIMP1), interleukin (IL)-18, regulated upon activation, normal T cell expressed and secreted (RANTES), P-Selectin, MMP9, and L-Selectin.Conclusions and Clinical RelevanceThe urine peptidomic and plasma protein analyses have the potential to improve SJIA care and suggest that SJIA urine peptide biomarkers may be an outcome of inflammation-driven effects on catabolic pathways operating at multiple sites.Electronic supplementary materialThe online version of this article (doi:10.1007/s12014-010-9058-8) contains supplementary material, which is available to authorized users.

Increased monocyte chemoattractant protein-1 levels indicating early vascular damage in lean young PCOS patients

Serum levels of monocyte chemoattractant protein-1 and C-reactive protein levels, as early signs of vascular damage and cardiovascular disease, were increased in young, lean patients with polycystic ovary syndrome. Serum monocyte chemoattractant protein-1 levels were positively correlated with serum LH, T, and C-reactive protein levels.

Functional characterization of the CC chemokine RANTES from Pekin duck ( Anas platyrhynchos)

RANTES (Regulated upon Activation, Normal T-cell Expressed and Secreted) is a key pro-inflammatory cytokine that belongs to the CC-group of chemokines. The present study was carried out to functionally characterize the previously identified RANTES homologue in domestic duck (GenBank Accession No. AY641435). Recombinant duck RANTES was expressed in Escherichia coli-based and HEK293T cell-based systems. A tRNA supplementation strategy was required to express the protein in E. coli due to the presence of rare codons. In biological assays using HEK293T cell-expressed protein, RANTES was found to mediate chemotaxis of DT-40 chicken B cells and primary duck splenocytes at a concentration of 0.505 μg/ml (0.6 μM). Immunostaining of the migrated splenocytes using anti-duck CD4 and CD8 monoclonal antibodies and subsequent flow cytometric analysis showed enhanced chemotaxis of CD8+ cells. The recombinant RANTES exhibited in vitro antiviral activity by inhibiting infection of chicken embryo fibroblast cells with duck enteritis virus (DEV) at the same concentration. The effect could be neutralized by rabbit anti-duck RANTES polyclonal serum. The mechanism seems to be direct on viral particles as evidenced by the need for co-incubation of RANTES with DEV prior to the infection for antiviral activity, and also by the enhanced binding of DEV to E. coli expressed purified RANTES on ELISA-based assays. Our results show that the duck RANTES has overlapping biological properties with its mammalian orthologue, and also has possible functional cross-reactivity with chicken immune cells indicated by the chemotaxis of DT-40 cells.

Opposite Action of Peroxisome Proliferator-activated Receptor-γ in Regulating Renal Inflammation: FUNCTIONAL SWITCH BY ITS LIGAND

Peroxisome proliferator-activated receptor-γ (PPARγ) agonists, a new class of antidiabetic agents, have been shown to possess antiinflammatory activity. In this study, we investigated the molecular mechanism by which PPARγ agonists inhibit proinflammatory cytokine expression in rat glomerular mesangial cells. Both natural and synthetic PPARγ agonists potently inhibited RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 expression induced by TNF-α in mesangial cells, which was dependent on NF-κB signaling. However, PPARγ agonists had little effect on TNF-α-triggered IκBα phosphorylation and its subsequent degradation, p65 phosphorylation, and nuclear translocation. In the absence of PPARγ ligand, TNF-α induced a physical interaction between nuclear p65 and PPARγ, as demonstrated by co-immunoprecipitation. Such an interaction was mediated by the C-terminal region of p65. Activation of PPARγ by its agonist prevented PPARγ·p65 complex formation. Chromatin immunoprecipitation assay revealed that TNF-α induced p65 binding to the cis-acting κB elements in rat RANTES promoter, whereas disruption of PPARγ·p65 by its agonist blocked p65 interaction with its cognate κB sites. Knockdown of PPARγ via siRNA strategy completely abolished TNF-α-mediated p65 binding to κB sites and negated RANTES induction, suggesting that unliganded PPARγ is obligatory for NF-κB signaling. Consistently, overexpression of PPARγ in the absence of its ligand sensitized mesangial cells to TNF-α stimulation. These results uncover a paradoxical action of the unliganded and ligand-activated PPARγ in regulating NF-κB signaling and demonstrate PPARγ ligand as a molecular switch that controls its ability to modulate inflammatory responses in opposite directions.

Effects of peritoneal fluid from endometriosis patients on the release of monocyte-specific chemokines by leukocytes

Chemokines have been implicated in the pathological process of endometriosis. We compared the effects of peritoneal fluid obtained from patients with endometriosis (ePF) and controls without endometriosis (cPF) on the release of monocyte-specific CC chemokines such as monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) by neutrophils, monocytes, and T cells. Moreover, we evaluated the correlation between the levels of chemokines in ePF and their release by these cells. Cells were obtained from healthy young volunteers and cultured with ePF (n = 12) or cPF (n = 8). The chemokine levels in the ePF and the supernatants of cultured cells with ePF were then measured by ELISA. There was a positive correlation between the levels of MCP-1 and MIP-1α in ePF. The addition of ePF to the cell cultures failed to increase the release of MCP-1, RANTES, and MIP-1α when compared to cPF, but the levels of RANTES in ePF were positively correlated with the release of RANTES by ePF-treated monocytes and T cells. Moreover, there was a positive correlation between the levels of RANTES and MIP-1α released by neutrophils and between the levels of MCP-1 and MIP-1α released by T cells. Finally, the levels of RANTES released by monocyte-derived macrophages and monocytes cultured with ePF were positively correlated. These findings suggest that monocytes, neutrophils, and T cells release differential levels of MCP-1, RANTES, and MIP-1α in response to stimulation with ePF.

Oxidized high‐density lipoprotein enhances inflammatory activity in rat mesangial cells

Inflammation is a mechanism of glomerular damage in chronic glomerulopathies, in which dyslipidaemia plays an important role. Unlike native high-density lipoprotein (HDL), oxidized HDL is thought to be an adverse factor in chronic ischaemic disease and may increase the production of inflammatory cytokines in atheromatous plaques and plasma, but the effect of oxidized HDL on mesangial cells remains unclear. Intracellular reactive oxygen species level was measured. The inflammatory and proapoptotic effects of oxidized HDL were detected in rat mesangial cells by measuring levels of tumour necrosis factor-alpha, regulated upon activation, normal T-cell expressed and secreted, monocyte chemoattractant protein-1, CXC chemokine ligand-1 and early apoptosis. The expression of mitogen-activated protein kinase (MAPK) (p38/MAPK, extracellular-regulated kinase/MAPK and c-Jun N-terminal kinase/MAPK), nuclear factor-kappaB activity and lipoprotein scavenger receptors (CD36, low-density lipoprotein receptor-1 and scavenger receptor BI) were also detected. Oxidized HDL enhanced reactive oxygen species production and upregulated expression of proinflammatory factors, including tumour necrosis factor-alpha, regulated upon activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 and CXC chemokine ligand-1 by rat mesangial cells dose in a dependent fashion. Incubation with oxidized HDL also increased rat mesangial cells apoptosis in a dose-dependent manner. These effects partly depended on scavenger receptors CD36 and low-density lipoprotein receptor-1, but not scavenger receptor BI. In addition, co-culture with oxidized HDL activated P38/MAPK, extracellular-regulated kinase (ERK)/MAPK and nuclear factor-kappaB (NF-kappaB). The results of the present study suggest that oxidized HDL enhanced proinflammatory properties in mesangial cells partly via CD36 and low-density lipoprotein receptor-1. MAPK and nuclear factor-kappaB pathways were involved in the process. The ability of oxidized HDL to negatively influence mesangial cell biology may represent an important mechanism of chronic kidney disease.

The role of RANTES as a crucial downstream cytokine in calcineurin‐dependent VSMC apoptosis stimulated by INFγ and CD40L

Many studies have suggested that VSMC (vascular smooth muscle cell) apoptosis plays a key role in destabilization and rupture of atherosclerotic plaques. Therefore protection for VSMCs from apoptosis is a promising approach to stabilize 'vulnerable' lesions. However, the mechanisms as to why VSMCs in the fibrous cap often appear as profilerated in early stages, but turn apoptotic in advanced stages, are still unknown. In the present study, using RNAi (RNA interference) technology and a CaN (calcineurin) antagonist, the correlation between CaN and RANTES (regulated upon activation, normal T-cell expressed and secreted) in cultured rat apoptotic VSMCs stimulated by IFNgamma (interferon gamma; 20 ng/ml) and CD40L (CD40 ligand; 100 ng/ml) was investigated. RANTES released from VSMCs in each group was measured by ELISA and its mRNA in VSMCs was determined by RT (reverse transcription)-PCR. The total activity and expression of CaN in VSMCs were detected by the zymochemistry method and Western blot analysis respectively. From the results of the present study it can be hypothesized that an elevated CaN concentration in endochylema, by the CD40-CD40L signal pathway, induces VSMC apoptosis accomplished by the overexpression of RANTES. Therefore RANTES is a potential target for treating vulnerable atherosclerotic plaques owing to its crucial downstream regulating role in CaN-dependent VSMC apoptosis.

Suppression of CC chemokine production and HMVEC chemotaxis by green tea extract

In the present study, we tested the efficacy of polyphenol‐containing green tea extract (GTE) in regulating CC chemokine production in human rheumatoid arthritis (RA) synovial fibroblasts and rat adjuvant‐induced arthritis (AIA), and human microvascular endothelial cell (HMVEC) chemotaxis. Pre‐incubation of RA synovial fibroblasts with GTE (2.5–40 μg/ml) inhibited interleukin‐1β (IL‐1β)‐induced monocyte chemoattractant protein (MCP)‐1/CCL‐2 and Regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5 production with an IC50 values of ~16.4 and ~7.5 μg/ml, respectively. Interestingly, GTE pre‐incubation significantly inhibited RANTES/CCL5‐induced HMVEC chemotaxis in a dose‐dependent manner. GTE administration (200 mg/kg/day p.o.) for 10 days markedly ameliorated AIA in rats as reflected by a decrease in articular index and ankle circumference in the GTE‐treated group by ~28% and ~38%, respectively, when compared to the PBS group. Suppression of arthritis was accompanied by a decrease in joint MCP‐1/CCL2 level and serum RANTES/CCL5 level. Inhibition of CC chemokine production and chemotaxis by GTE may be one potential mechanism to limit the overall inflammation and joint destruction in RA.

Local Production of Inflammatory Mediators During Childhood Parainfluenza Virus Infection

To describe the clinical manifestations of parainfluenza virus (PIV) infection and to characterize biochemical markers of PIV disease severity. We reviewed the medical records of 165 children who had a nasal wash culture positive for PIV at our institution between 1998 and 2008. Nasal wash samples were assayed for 26 inflammatory mediators using Luminex bead proteomics. A total of 153 patients, ages 2 weeks to 12 years, with single virus infection were included in our final analysis. Fifty-two patients were infected with PIV1, 19 with PIV2, 74 with PIV3, and 8 with PIV4. Lower respiratory tract infection (LRTI) was diagnosed in 67 (44%) patients, 21 (14%) had laryngotracheobronchitis, and 49 (32%) had an upper respiratory infection other than laryngotracheobronchitis. LRTI was diagnosed in 54% of patients infected with PIV3, 35% of those infected with PIV1, 26% of those with PIV2, and 50% of those with PIV4. Compared with uninfected control patients, PIV-infected patients had higher nasal wash concentrations of interleukin-6, CX-chemokine ligand 8 (CXCL8 or interleukin-8), CCL3 (macrophage inflammatory protein-1alpha), CCL4 (macrophage inflammatory protein-1beta), CXCL9 (monokine induced by interferon gamma), and CCL5 (regulated upon activation, normal T cell expressed and secreted (RANTES). Patients with LRTI, moderate or severe illness, and PIV 1 or 3 (respirovirus) infection had higher nasal wash concentrations of CXCL8 when compared with patients with upper respiratory infection, mild illness, or PIV 2 and 4 (rubulavirus) infection (P < 0.05). PIV infection causes a spectrum of illnesses associated with the expression and release of several proinflammatory mediators. Of note, elevated concentrations of CXCL8 in nasal wash samples are associated with more severe forms of PIV disease.

Regulated upon activation normal T-cell expressed and secreted originating from the epididymis differentially associates with viable and defective spermatozoa

To investigate the expression and cellular distribution of regulated upon activation normal T-cell expressed and secreted (RANTES) in the male reproductive system. Basic research. University academic medical center. Three adult male organ donors. None. Reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization, immunohistochemical staining, and immunofluorescence staining were used to examine the distribution of RANTES in human and mouse epididymis. Western blot was used to quantitate the levels of RANTES expression in mouse epididymis on postnatal days. Immunofluorescence staining was applied to detect RANTES association with spermatozoa from mouse epididymis. The location of RANTES was restricted to ciliated cells of the efferent duct and apical, narrow, and basal cells of the epididymal ducts, in both humans and mouse. RANTES-positive basal cells were only identified in the epididymal ducts in humans. The signals of RANTES were first detected on day 28 and increased during mouse sexual maturation. We also observed that RANTES was bound on both normal and defective epididymal sperm, but in different patterns. RANTES is constitutively expressed in the epididymis and secreted into the lumen of epididymis throughout sexual maturity, and differentially associates with viable and defective spermatozoa.

Modulation of the bovine innate immune response by production of 1α,25-dihydroxyvitamin D3 in bovine monocytes

In cattle, the kidney has been the only known site for production of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] from 25-hydroxyvitamin D3 [25(OH)D3] by 1α-hydroxylase (1α-OHase). Based on human studies, it was hypothesized that bovine monocytes could produce 1,25(OH)2D3 upon activation and 1,25(OH)2D3 would regulate expression of vitamin D–responsive genes in monocytes. First, the effects of 1,25(OH)2D3 on bovine monocytes isolated from peripheral blood were tested. Treatment of nonstimulated monocytes with 1,25(OH)2D3 increased expression of the gene for the vitamin D 24-hydroxylase (24-OHase) enzyme by 51±13 fold, but 1,25(OH)2D3 induction of 24-OHase expression was blocked by lipopolysaccharide (LPS) stimulation. In addition, 1,25(OH)2D3 increased the gene expression of inducible nitric oxide synthase and the chemokine RANTES (regulated upon activation, normal T-cell expressed and secreted) in LPS-stimulated monocytes 69±13 and 40±12 fold, respectively. Next, the ability of bovine monocytes to express 1α-OHase and produce 1,25(OH)2D3 was tested. Activation of monocytes with LPS, tripalmitoylated lipopeptide (Pam3CSK4), or peptidoglycan caused 43±9, 17±3, and 19±3 fold increases in 1α-OHase gene expression, respectively. Addition of 25(OH)D3 to LPS-stimulated monocytes enhanced expression of inducible nitric oxide synthase and RANTES and nitric oxide production in a dose-dependent manner, giving evidence that activated monocytes convert 25(OH)D3 to 1,25(OH)2D3. In conclusion, bovine monocytes produce 1,25(OH)2D3 in response to toll-like receptor signaling, and 1,25(OH)2D3 production in monocytes increased the expression of genes involved in the innate immune system. Vitamin D status of cattle might be important for optimal innate immune function because 1,25(OH)2D3 production in activated monocytes and subsequent upregulation of inducible nitric oxide synthase and RANTES expression was dependent on 25(OH)D3 availability.

Association between regulated upon activation, normal T cells expressed and secreted (RANTES) -28C/G polymorphism and asthma risk - A Meta-Analysis

Regulated upon activation, normal T-cell expressed and secreted (RANTES) is one of the most extensively studied C-C chemokines in allergic inflammation. A growing body of evidence suggests that many cell types present in asthmatic airways have the capacity to generate RANTES, which directly supported the potential role of RANTES in asthma. A number of studies have evaluated the functional polymorphism -28C/G in the RANTES promoter region, which had been found to affect the transcription of the RANTES gene, in relation to asthma susceptibility. However, the results remain conflicting rather than conclusive. This meta-analysis on 1894 asthma cases and 1766 controls for -28C/G from 9 published case-control studies showed that the variant allele -28G was associated with significantly increased risk of asthma (GG+CG vs CC: OR=1.24, 95%CI=1.08-1.41) without any between-study heterogeneity.In the stratified analysis by asthma type, age and ethnicity, we found that the increased asthma risk associated with -28G/C polymorphism was more evident in children (OR=1.24, 95%CI=1.06-1.45), Asian group (OR=1.27, 95%CI=1.04-1.56) and African group (OR=1.72, 95%CI=1.07-2.78). These results suggest that RANTES -28G/C polymorphism may contribute to asthma development, especially in children and in Asian population. Additional well-designed large studies were required for the validation of this association.

Wild Panax Ginseng (Panax ginsengC.A. Meyer) Protects Against Methotrexate–Induced Cell Regression by Enhancing the Immune Response in RAW 264.7 Macrophages

Many traditional herbal medicines have been re-evaluated to determine whether they enhance immune responses. In this study, the possible use of wild Panax ginseng (WPG) for enhancement of host immunity in chemotherapy was investigated. In the cell proliferation assay, WPG significantly enhanced the proliferation of RAW 264.7 macrophages and protected against cell regression in macrophages treated with methotrexate (MTX). WPG induced the production of nitric oxide and the expression of inducible nitric oxide synthase and cyclooxygense-2 mRNA. Furthermore, WPG enhanced the production of cytokines including interleukin (IL)-1alpha, IL-1beta, IL-6, tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor, and chemokines such as macrophage chemotactic protein-1 and regulated upon activation, normal T-cell expressed and secreted (RANTES), regardless of MTX co-administration. Taken together, these results provide the first evidence that WPG triggers immune responses through the prevention of macrophage cell regression caused by MTX and functional activation of macrophages.

Circulating β Chemokine and MMP 9 as Markers of Oxidative Injury in Extremely Low Birth Weight Infants

Matrix metalloproteinases (MMPs) and chemokines seem to be induced by hyperoxia in preclinical studies. We hypothesized that O2 exposure immediately after birth is associated with altered blood spot MMP 9 and beta chemokine concentrations. The following analytes were measured on blood spots on d 1 and 3 of life, using luminex technology in 1059 infants (birth weights <1000 g) in the NICHD Neonatal Research Network: MMP 9, monocyte chemoattractant protein 1 (MCP 1), macrophage inflammatory proteins (1alpha and beta), and regulated upon activation, normal t cell expressed and secreted (RANTES). Infants administered O2 continually from 6 to 24 h of life (n = 729), when compared with those with <6 h exposure (n = 330), had significantly lower mean birth weight and higher rate of respiratory distress syndrome (p < 0.002). On d 3, MCP 1 was higher and RANTES lower among infants with early prolonged O2 exposure. After adjusting for covariates, prolonged early O2 exposure retained a statistically significant association with higher MCP 1 on d 3 (p = 0.003). The consistent association between O2 exposure and MCP 1 among extremely preterm infants suggests that further investigation of its role in oxidative injury is warranted.

Green tea extract inhibits chemokine production, but up-regulates chemokine receptor expression, in rheumatoid arthritis synovial fibroblasts and rat adjuvant-induced arthritis

Evaluation of the efficacy of green tea extract (GTE) in regulating chemokine production and chemokine receptor expression in human RA synovial fibroblasts and rat adjuvant-induced arthritis (AIA). Fibroblasts isolated from human RA synovium were used in the study. Regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5, monocyte chemoattractant protein (MCP)-1/CCL2, growth-regulated oncogene (GRO)alpha/CXCL1 and IL-8/CXCL8 production was measured by ELISA. Western blotting was used to study the phosphorylation of protein kinase C (PKC)delta and c-Jun N-terminal kinases (JNK). Chemokine and chemokine receptor expression was determined by quantitative RT-PCR. The benefit of GTE administration in rat AIA was determined. GTE (2.5-40 microg/ml) inhibited IL-1beta-induced MCP-1/CCL2 (10 ng/ml), RANTES/CCL5, GROalpha/CXCL1 and IL-8/CXCL8 production in human RA synovial fibroblasts (P < 0.05). However, GTE inhibited MCP-1/CCL2 and GROalpha/CXCL1 mRNA synthesis in RA synovial fibroblasts. Furthermore, GTE also inhibited IL-1beta-induced phosphorylation of PKCdelta, the signalling pathway mediating IL-1beta-induced chemokine production. Interestingly, GTE preincubation enhanced constitutive and IL-1beta-induced CCR1, CCR2b, CCR5, CXCR1 and CXCR2 receptor expression. GTE administration (200 mg/kg/day p.o.) modestly ameliorated rat AIA, which was accompanied by a decrease in MCP-1/CCL2 and GROalpha/CXCL1 levels and enhanced CCR-1, -2, -5 and CXCR1 receptor expression in the joints of GTE administered rats. Chemokine receptor overexpression with reduced chemokine production by GTE may be one potential mechanism to limit the overall inflammation and joint destruction in RA.