High Monocyte Chemotactic Protein-1 Research Articles

Risk factors of acute kidney injury induced by multiple wasp stings

In Asia, acute kidney injury (AKI) induced by wasp stings is common; however, the pathophysiological mechanisms involved remain unclear. To evaluate the mechanisms associated with AKI induced by wasp stings, we conducted a retrospective cohort study that assessed blood and urinary samples from 112 patients with hospital admissions resulting from wasp stings. These samples were divided into those with AKI and without AKI as described in the Kidney Disease Improving Global Outcomes (KDIGO) database. Of the patients, 48.2% presented with an elevated number of leukocytes (median 19.9 vs. 15.8 × 109/L), serum creatinine (median 122.0 vs. 66.0 μmol/L), alanine aminotransferase (ALT) (median 176 vs. 32 U/L), aspartate aminotransferase (AST) (median 402 vs. 37 U/L), lactate dehydrogenase (LDH) (median 3076.0 vs. 300.0 U/L), creatine kinase (CK) (median 9990.0 vs. 261.0 U/L), creatine kinase myocardial band (CK-mb) (median 200.0 vs. 29.5 U/L), activated partial thromboplastin time (APTT) (median 70.0 vs. 42.5s), prothrombin time (PT) (median 15.0 vs. 12.5s), myoglobin (median 2200.0 vs. 78.0 ng/mL), proteinuria (51.9% vs. 17.2% ≥ 1+), and urinary monocyte chemotactic protein-1 (MCP-1) (median 432.0 vs. 177.0 pg/mL), and subsequently developed AKI. As determined by multivariate logistic regression analysis, elevated leukocytes (>10 × 109/L) [OR 1.12 (95% CI 1.02–1.23)], high myoglobin (>1200 ng/mL) [OR 18.51 (95% CI 1.51–132.27)], and high urinary MCP-1 (>200 pg/mL) [OR 5.42 (95% CI 1.27–30.39)] on admission were independent risk factors for AKI. At admission, baseline values for ALT, aspartate aminotransferase (AST), LDH, CK-mb, APTT, PT, and proteinuria were higher for those who later died as well as for those who developed end-stage renal disease (ESRD). No patients without AKI died or developed ESRD. The present study explored the pathophysiology of AKI induced by wasp stings based on the findings of risk factors as well as factors related to outcomes. An understanding of AKI induced by wasp stings allows better treatment options and clinical management for wasp stings patients.

The Mechanism of miR-192 in Regulating High Glucose-Induced MCP-1 Expression in Rat Glomerular Mesangial Cells.

Although the pathogenetic mechanism of Diabetic Kidney Disease (DKD) has not been elucidated, an inflammatory mechanism may be a potential contributor. Monocyte chemotactic protein-1 (MCP-1) is suggested to be implicated in the development of DKD by playing a role in the infiltration of monocyte/macrophage. The aim of this study was to investigate the expression of MCP-1 under high glucose conditions, as well as the effects of microRNA-192 (miR-192) under these conditions, and to study the regulatory mechanism of MCP-1 in DKD. Rat glomerular mesangial cells were cultured in high glucose or isotonic mannitol. The messenger RNA(mRNA) expression of miR-192, miR-200b, miR-200c, E-box-binding homeobox 1 (Zeb1), and MCP-1 was then detected by real-time PCR, and the protein expression of Zeb1 and MCP- 1 was assessed by western blotting. The rat mesangial cells were transfected with an miR-192 inhibitor, NC inhibitor , and transfected with siRNA Zeb1, siNC. The cells were then cultured in high glucose to detect the mRNA expression of miR-192, miR-200b, miR-200c, Zeb1, and MCP-1 using realtime PCR, and Zeb1 and MCP-1 protein expression were determined by western blotting. MiR-192, miR-200b, miR-200c, and MCP-1 were overexpressed, whereas Zeb1 was downregulated when cultured in high glucose (P < 0.05). After transfection with an miR-192 inhibitor, the expression of miR-192, miR-200b, miR-200c, and MCP-1 was downregulated, whereas Zeb1 was increased, and these differences were statistically significant (P < 0.05). The observed changes in the expression in the NC inhibitor transfection group were similar to that of non-transfected cell lines. Silencing the expression of Zeb1 resulted in a significant increase in the expression of miR-192, miR- 200b, miR-200c, and MCP-1 (P < 0.05). The observed changes in the SiNC transfection group were similar to those of non-transfected cell lines. MiR-192 expression was upregulated to increase the expression of inflammatory factor MCP-1 by inhibiting the expression of Zeb1, which was mediated by breaking the regulatory loop of Zeb1 and miR-200b/c in rat mesangial cells cultured in high glucose.

SAT-197 Functional Cross-Talk Between MCP-1 and Integrin Linked Kinase Is Required for Endometriosis Disease Progression

Development of painful invasive endometriotic lesions is usually a combined function of the chronic inflammation and active sequential cellular events such as migration, cell adhesion, proliferation, colonization, and invasion in endometriosis. An elevated level of monocyte chemotactic protein-1 (MCP-1) in serum and peritoneal fluid has been reported in endometriosis. Further, Integrin-Linked Kinase (ILK) communicates with extracellular signals and regulates the sequential cellular events in uterine and ovarian cancer. The functional cross-talk of MCP-1 with ILK in the immune cells leads to the high MCP-1 production and increased ILK activity. However, the role of the elevated MCP-1 level and its functional interaction with ILK in the endometriosis development is not explored yet. In order to investigate this, we used the surgically induced heterologous mouse model of endometriosis and externally treated with MCP-1 intraperitoneally for two weeks. Our results demonstrated that MCP-1 boosted the growth of endometriotic lesions mediated through ILK, FAK, VAV and RAC1 signaling axis in endometriosis. In addition, in vivo pharmacological inhibition of ILK by CPD22 restricted the growth of endometriotic lesions in mice. Flow cytometric and inflammatory cytokines profiling in the peritoneal fluid demonstrated that ILK was involved in the MCP-1 mediated macrophageF4/80+ recruitment and inflammatory response in order to support the growth of endometriotic lesions. Inhibition of ILK induced the anti-inflammatory cytokine IL-10 and concomitantly suppressed the pro-inflammatory cytokines MCP-1, TNF-α and IL-10 levels in peritoneal fluid. In vitro studies on human ovarian cystic endometriosis cells (Hs832(C).T) and normal endometrial stromal cells (T-HESCs) revealed that MCP-1 accelerated the adhesion (on collagen and fibronectin substratum), colonization, migration and 3D-spheroids formation and invasion. As the basal level of CCR2, an MCP-1 receptor, expression was higher in ovarian endometriotic cells than the normal endometrial stromal cells giving the hint for the role of MCP-1 in endometriosis. Interestingly, the siRNA mediated knockdown of ILK renders the MCP-1 induced nuclear translocation of phosphorylated ILK and also reduced these accelerated cellular events. Taken together, our results provide compelling evidence that the functional cross-talk between MCP-1 and ILK drives endometriotic disease progression.

Combined cellular and soluble mediator analysis for improved diagnosis of vitreoretinal lymphoma.

PurposePrimary vitreoretinal lymphoma [(P)VRL]) is a rare malignancy of the eye localized in the retina, vitreous or choroid. Here, we aim to determine the value of the combination of innovative diagnostic methods for accurate differentiation between (P)VRL and non‐(P)VRL in patients with suspect uveitis or vitritis.MethodsMulticolour flow cytometric immunophenotyping of cells in the vitreous samples was performed using the EuroFlow small sample tube. Additionally, cytokines/chemokines and growth factors were measured in the vitreous specimens using a multiplex immunoassay. Data were evaluated in predefined clinical subgroups using omniviz unsupervised Pearson's correlation visualization and unsupervised heatmap analysis.ResultsA total of 53 patients were prospectively included in the period 2012–2015. In the (P)VRL subgroup (n = 10), nine cases showed aberrant surface membrane immunoglobulin (SmIg) light chain expression. In the non‐(P)VRL group (n = 43) clearly skewed SmIg light chain expression was observed in two multiple sclerosis‐related uveitis cases, but not in other uveitis types. Soluble mediator measurement revealed high interleukin (IL)‐10/IL‐6 ratios, and high IL‐1RA levels in 9/10 (P)VRL cases, but not in any non‐(P)VRL case. Further correlation and heatmap analysis revealed a minimal signature of cellular parameters (CD19+ B cells, aberrant SmIg light chain expression) and cytokine parameters (IL‐10/IL‐6 ratio >1, high IL‐10, high IL‐1 RA, high monocyte chemotactic protein‐1, high macrophage inflammatory protein‐1β) to reliably distinguish (P)VRL from non‐(P)VRL.ConclusionHere, we show the power of a combined cellular and proteomics strategy for detecting (P)VRL in vitreous specimens, especially in cases with minor cellular (P)VRL infiltrates.

A prospective study of soluble receptor for advanced glycation end products and adipokines in association with pancreatic cancer in postmenopausal women.

Advanced glycation end products (AGEs) dysregulate adipokines and induce inflammation by binding to their adipocyte receptor (RAGE). Soluble RAGE (sRAGE) prevents AGEs/RAGE signaling. We performed a nested case–control study of the association between sRAGE, adipokines, and incident pancreatic cancer risk in the prospective Women's Health Initiative Study. We individually matched controls (n = 802) to cases (n = 472) on age, race, and blood draw date. We evaluated serum concentrations of sRAGE, adiponectin, leptin, monocyte chemotactic protein 1 (MCP1), and plasminogen activator inhibitor‐1 (PAI1) using immunoassay. We used conditional logistic regression model to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for pancreatic cancer over biomarker quartiles (Q1–Q4). We used principal component analysis to create two composite biomarkers and performed a confirmatory factor analysis to examine the association between composite biomarker scores (CBS) and pancreatic cancer risk. Baseline serum sRAGE concentrations were inversely associated with pancreatic cancer risk (aORQ4 vs. Q1 = 0.70, 95% CI: 0.50–0.99). High MCP1 (aOR Q4 vs. Q1 = 2.55, 95% CI: 1.41–4.61) and the higher CBS including MCP1, PAI1, and leptin (aORQ4 vs. Q1 = 1.82, 95% CI = 1.04–3.18) were also associated with increased pancreatic cancer risk among women with BMI <25 kg/m2 (P values for interaction <0.05). We found an inverse association between prediagnostic sRAGE concentrations and risk of incident pancreatic cancer in postmenopausal women. A proinflammatory CBS was associated with increased risk only in women with normal BMI. MCP1 was not modulated by sRAGE.

Monocyte Chemotactic Protein 1 (MCP-1) Modulates Pro-Survival Signaling to Promote Progression of Head and Neck Squamous Cell Carcinoma

BackgroundMonocyte chemotactic protein-1 (MCP-1) recruits monocytes and macrophages to inflammation sites, and inflammatory infiltration correlates with the progression of head and neck squamous cell carcinoma (HNSCC). This study aims to determine whether MCP-1 expression is related to HNSCC malignancy and patient survival. We also investigated the relationship between MCP-1 expression and the phosphorylation state of the pro-survival pathway factors Akt, ERK, and STAT3.MethodsExpression of MCP-1 and related proteins in HNSCC cell lines was investigated using western blotting. HNSCC patients (34) without distant metastasis at diagnosis were recruited for tissue specimen evaluation of MCP-1 expression and clinical outcomes. The relationship between MCP-1 expression and survival was evaluated using the Cox proportional hazard model with stepwise selection.ResultsHigh-grade HNSCC cell lines were found to have higher levels of active Akt, ERK, and/or STAT3 than did lower grade cell lines under serum-free condition. OCSL, the most malignant cell line, had the highest level of endogenous MCP-1. Administration of exogenous recombinant MCP-1 increased phosphorylation of Akt, ERK, and STAT3 in a dose- and time-dependent manner and increased cellular resistance to serum starvation. Inhibition of Akt, ERK, or STAT3 reduced cell growth and caused cell death. Long-term survival of HNSCC patients was negatively associated with the histological intensity of MCP-1, implicating MCP-1 as a potential prognostic marker for HNSCC.ConclusionsThese results suggest that overexpressed MCP-1 in cancer cells may promote HNSCC progression through upregulating pro-survival signaling pathways. High cellular MCP-1 expression is related to poor overall survival rate in HNSCC patients.

Cerebrospinal fluid inflammatory markers in Parkinson’s disease – Associations with depression, fatigue, and cognitive impairment

Neuroinflammation may be involved in the pathophysiology of Parkinson's disease (PD) and specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. The aim of this study was to measure inflammatory markers in cerebrospinal fluid (CSF) samples from PD patients and a reference group, and to investigate correlations between non-motor symptoms and inflammation. We quantified C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein 1-β in CSF samples from PD patients (N=87) and the reference group (N=33). Sixteen of the PD patients had a dementia diagnosis (PDD). We assessed symptoms of fatigue, depression, anxiety and cognitive function using the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and the Mini Mental State Examination, respectively. There were no significant differences in mean levels of inflammatory markers between PD patients and the reference group. After controlling for age, gender and somatic illness, patients with PDD had significantly higher levels of CRP compared to non-demented PD patients (p=0.032) and the reference group (p=0.026). Increased levels of inflammatory markers in CSF were significantly associated with more severe symptoms of depression, anxiety, fatigue, and cognition in the entire PD group. After controlling for PD duration, age, gender, somatic illness and dementia diagnosis, high CRP levels were significantly associated with more severe symptoms of depression (p=0.010) and fatigue (p=0.008), and high MCP-1 levels were significantly associated with more severe symptoms of depression (p=0.032). Our results indicate that non-motor features of PD such as depression, fatigue, and cognitive impairment are associated with higher CSF levels of inflammatory markers.

Monocyte Chemotactic Protein-1 as a Potential Biomarker for Early Anti-Thrombotic Therapy after Ischemic Stroke

Inflammation following ischemic brain injury is correlated with adverse outcome. Preclinical studies indicate that treatment with acetylsalicylic acid + extended-release dipyridamole (ASA + ER-DP) has anti-inflammatory and thereby neuroprotective effects by inhibition of monocyte chemotactic protein-1 (MCP-1) expression. We hypothesized that early treatment with ASA + ER-DP will reduce levels of MCP-1 also in patients with ischemic stroke. The EARLY trial randomized patients with ischemic stroke or TIA to either ASA + ER-DP treatment or ASA monotherapy within 24 h following the event. After 7 days, all patients were treated for up to 90 days with ASA + ER-DP. MCP-1 was determined from blood samples taken from 425 patients on admission and day 8. The change in MCP-1 from admission to day 8 did not differ between patients treated with ASA + ER-DP and ASA monotherapy (p > 0.05). Comparisons within MCP-1 baseline quartiles indicated that patients in the highest quartile (>217–973 pg/mL) showed improved outcome at 90 days if treated with ASA + ER-DP in comparison to treatment with ASA alone (p = 0.004). Our data does not provide any evidence that treatment with ASA + ER-DP lowers MCP-1 in acute stroke patients. However, MCP-1 may be a useful biomarker for deciding on early stroke therapy, as patients with high MCP-1 at baseline appear to benefit from early treatment with ASA + ER-DP.

High glucose stimulates TNFα and MCP-1 expression in rat microglia via ROS and NF-κB pathways

To investigate whether high glucose stimulates the expression of inflammatory cytokines and the possible mechanisms involved. ELISA and real-time PCR were used to determine the expression of the inflammatory factors, and a chemiluminescence assay was used to measure the production of reactive oxygen species (ROS). Compared to low glucose (10 mmol/L), treatment with high glucose (35 mmol/L) increased the secretion of tumor necrosis factor (TNF)α and monocyte chemotactic protein-1 (MCP-1), but not interleukin (IL)-1β and IL-6, in a time-dependent manner in primary cultured rat microglia. The mRNA expression of TNFα and MCP-1 also increased in response to high glucose. This upregulation was specific to high glucose because it was not observed in the osmotic control. High-glucose treatment stimulated the formation of ROS. Furthermore, treatment with the ROS scavenger NAC significantly reduced the high glucose-induced TNFα and MCP-1 secretion. In addition, the nuclear factor kappa B (NF-κB) inhibitors MG132 and PDTC completely blocked the high glucose-induced TNFα and MCP-1 secretion. We found that high glucose induces TNFα and MCP-1 secretion as well as mRNA expression in rat microglia in vitro, and this effect is mediated by the ROS and NF-κB pathways.

Correlations between Serum Monocyte Chemotactic Protein-1 Levels, Clinical Prognostic Factors, and HER-2/neu Vaccine-Related Immunity in Breast Cancer Patients

We studied serum monocyte chemotactic protein-1 (MCP-1) levels in breast cancer patients in relationship to their clinicopathologic variables and immune response to a /neu E75 vaccine. We measured MCP-1 levels in 32 /neu(+) breast cancer patients before and after vaccination with a /neu E75 peptide + granulocyte macrophage colony-stimulating factor vaccine. Clinical prognostic variables were collected. Vaccine-specific immunologic responses were monitored. Serum MCP-1 levels >250 pg/mL (MCP-high) correlated with favorable prognostic variables. MCP-high patients compared with MCP-low (<250 pg/mL) patients showed statistically significant later onset of disease, earlier stage of disease, fewer nodal metastasis, and less chemotherapy. MCP-high patients had increased levels of preexisting immunity when compared with MCP-low patients (69% versus 21%; P = 0.02). However, MCP-low patients showed higher inducible levels of MCP-1 compared with MCP-high patients (median increase, 41% versus 0%; P = 0.001) after vaccination. Moreover, MCP-low patients with >50% increase in MCP-1 levels (response-high) had worse clinical prognostic variables compared with patients with <50% increase (response-low). Response-high patients had statistically significant more poorly differentiated tumors, later stage of disease, and higher percentage of large tumors. Patients with >30% postvaccination MCP-1 increase also showed significant increases in E75-specific CD8(+) T-cells (0.05% versus 0.38%; P = 0.03) in response to vaccination. High serum MCP-1 levels in breast cancer patients correlate with favorable prognostic variables and increased preexisting /neu immunity. E75 vaccination induces the largest MCP-1 response in patients with unfavorable clinicopathologic variables. Therefore, low serum MCP-1 levels may identify patients with worse prognosis and those most likely to benefit from this vaccination.

The -2518 Promotor Polymorphism in the MCP-1 Gene Is Associated with Systemic Sclerosis

Factors influencing the initiation or progression of sclerosis in patients with systemic sclerosis (SSc) are poorly understood. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine, which is upregulated in fibroblasts during development of sclerosis. In this study, we investigated the frequency of the functional -2518G MCP-1 promoter polymorphism in 18 patients with SSc and 139 healthy controls. In the lesional skin of the same SSc patients, expression of MCP-1 protein was examined by immunohistochemistry. To investigate a genotype/phenotype correlation, basal as well as tumor necrosis factor (TNF)-induced MCP-1 expression was analyzed in fibroblasts isolated from the skin of SSc patients with different MCP-1 genotypes by quantitative RT-PCR and ELISA. Genotyping for the -2518 (A/G) MCP-1 promotor polymorphism showed that GG homozygotes were significantly more frequent in patients with SSc than in controls (28%vs 6%). Results of immunohistochemistry revealed that MCP-1 was expressed in keratinocytes, infiltrating inflammatory cells, fibroblasts, and endothelial cells in scleroderma skin, whereas normal control skin showed no MCP-1 expression. MCP-1 expression in fibroblasts from GG-homozygote individuals tended to be stronger as compared to AG or AA genotypes. Furthermore, basal as well as TNF-induced MCP-1 expression of fibroblasts isolated from a GG-homozygote SSc patient was significantly higher than MCP-1 expression of fibroblasts isolated from heterozygote or AA-homozygote donors. The A -2518G polymorphism of the MCP-1 gene appears to affect MCP-1 expression of skin fibroblasts of patients with SSc. In accordance, the G/G genotype may predispose patients to SSc.

Significance of monocyte chemotactic protein-1 and thymidine phosphorylase in angiogenesis of human cardiac myxoma.

Angiogenesis is indispensable to tumor development and proliferation. The aim of this study was to investigate whether the expression of monocyte chemotactic protein-1 (MCP-1) and of thymidine phosphorylase (TP) correlates with the angiogenesis and clinicopathologic features in cardiac myxoma. Paraffin-embedded specimens of 17 resected cardiac myxomas were immunohistochemically stained for MCP-1, CC chemokine receptor-2 (CCR-2), TP, CD31, and CD68. Correlations among MCP-1 expression, TP expression, microvessel count (determined by CD31 staining), macrophage count (determined by CD68 staining), and the clinicopathologic features of the patients were analyzed statistically. Immunohistochemical analysis revealed that MCP-1 and TP were expressed in myxoma cells, as well as in stromal cells such as infiltrating cells, fibroblast-like cells and endothelial cells. CCR-2 was abundantly expressed in stromal infiltrating cells in all myxomas and occasionally in the endothelial cells. In the tumor stroma, the major source of MCP-1, TP and CCR-2 was macrophages, and the sites of positive staining for MCP-1, TP and CCR-2 matched in most of the myxomas. Statistical analysis revealed that the proportions of MCP-1-positive myxoma and stromal cells, and TP-positive myxoma and stromal cells significantly correlated with increased microvessel count. The proportions of MCP-1-positive myxoma and stromal cells significantly correlated with the proportion of TP-positive stromal cells. The mean microvessel count in myxomas with both high tumor and high stromal MCP-1 or TP expression was significantly higher than that in myxomas with low tumor and low stromal MCP-1 or TP expression. Small tumors (< or =55 mm in diameter) exhibited high MCP-1 or TP expression, and the microvessel count in small tumors was significantly higher than in large myxomas. Although the difference was not significant, myxomas with both high tumor and high stromal MCP-1 expression had a higher macrophage count than other myxomas. These results indicate that in cardiac myxoma, MCP-1 and TP may be regarded as important angiogenic signals accompanying growth.

Characterization of monocyte chemotactic protein-1 binding to human monocytes

Monocyte chemotactic protein-1 (MCP-1) stimulates chemotaxis of peripheral blood monocytes. In order to understand the biologic basis of this specific activity, binding studies of 125I-MCP-1 were undertaken. MCP-1 showed saturable binding to monocytes. Scatchard analysis of the monocyte binding data indicate that there are approximately 1,600 high affinity binding sites per monocyte with a Kd = 1.1 nM. Studies with synthetic peptides constructed according to the MCP-1 amino acid sequence indicate that a synthetic peptide, MCP-1[13–35], stimulates monocyte migration and competes with native MCP-1 for binding sites. Inhibition of MCP-1 binding was tested with chemotactic connective tissue proteins. No inhibition of MCP-1 binding was observed with either collagen, elastin-derived peptides or fibronectin. These results identify a single class of unique high affinity MCP-1 binding sites that are likely to recognize a peptide domain on MCP-1 which include the amino acids within the region, 13–35.