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Abstract Background Inflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease. Methods This study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC (n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student’s t-test. Results The results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6, IL-8, and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell. Conclusions This study identified the overexpression of IL-6, IL-8, and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC.

The monocyte chemo-attractant protein-1 (MCP-1) is one of the proinflammatory cytokines. It controls the passage and infiltration of monocytes, macrophages, natural killers, and T cells into the sites of inflammation. The aim of this study is to inspect the role of MCP-1 in maternal metabolic, physiological changes and pregnancy complications like gestational diabetes mellitus, dyslipidemia, and hypertension to develop pharmaceutical strategies for these complications. This study included ninety Iraqi women divided into three groups: thirty pregnant women in their first trimester as the P1 group; thirty pregnant women in their third trimester as the P2 group; and thirty healthy non-pregnant women as the control or C group. Serum concentrations of MCP-1 were analyzed by the ELISA technique (sandwich principle). Fasting plasma glucose (FPG), C-reactive protein (CRP), fasting serum insulin (FSI), glycosylated hemoglobin (HbA1c), lipid profile, systolic, diastolic blood pressure, liver function enzymes ALT, AST and anthropometric parameters were measured. Our results revealed that serum MCP-1 significantly declined in the first trimester (P1) compared to the C group (p<0.05) and non-significantly declined in the third trimester (P2) compared to that in the C group, while there was a significant difference in serum MCP-1 between the P1 and P2 groups (p<0.05 ). Serum CRP showed a highly significant increase in the P1 and P2 groups compared to the C group at (p<0.01). There is a highly significant difference between the P1 and P2 groups (p<0.01). Serum MCP-1 had a significant positive correlation with body mass index (BMI), body fat percentage (BF %), systolic blood pressure (SBP) and C-reactive protein (CRP) in the P2 group (p<0.05). No significant differences in FPG or HbA1C were found between all the studied groups. Lipid parameters: TC, TG, LDL, and VLDL showed a highly significant increase in the P2 group compared to the C and P1 groups (p<0.01). HDL showed a highly significant decrease in the P2 group compared to the C group (p<0.01), while it was only significantly decreased in the P2 group compared to the P1 group (p<0.05). Depending on these results, we found that serum MCP-1 declines in pregnancy, the BMI, BF%, and the contractile arterial blood pressure (SBP) have a positive correlation with MCP-1 in late pregnancy, and the inflammation marker (CRP) has an independent association with MCP-1 in early gestation. [ABSTRACT FROM AUTHOR]

Background: Inflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease. Methods: This study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC (n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student's t-test. Results: The results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6, IL-8, and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell. Conclusions: This study identified the overexpression of IL-6, IL-8, and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC. [ABSTRACT FROM AUTHOR]

Chronic kidney diseases occur as result of exposure to wide range of deleterious agents as environmental pollutants, toxins and drug. Currently, there is no effective protective therapy against renal damage, fibrosis and its sequel of end stage renal disease. Platelet-rich plasma (PRP) has a progressively gained consideration in wound healing, repair/regeneration of damaged tissues and conservation of organ function. However, its impact on thioacetamide (TAA) induced chronic renal damage has not been elucidated yet. So, the present study was carried out to evaluate the possible protective and regenerative effect of PRP against TAA induced renal damage and their potential underlying mechanism. PRP treatment improved redox state, renal function disturbed histologicl features; decreased monocyte chemo-attractant protein-1 (MCP-1) level; increased Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) marker of mitochondrial biogenesis and metabolism; cyclic adenosine monophosphate (cAMP); hepatocyte growth factor (HGF) and autophagy protein beclin-1 level. In addition, PRP treatment decreased apoptosis and fibrosis as evidenced by decreased active caspase3 and α-SMA expression and immunoreactivity, respectively. In conclusion, PRP could potentially protect against TTA-induced chronic kidney damage by alleviating oxidative stress, improving, mitochondrial biogenesis, autophagy, disruption of the inflammatory, apoptotic and fibrotic response induced by TTA.

Graphical abstract Highlights • PRP improved kidney function and disturbed kidney architecture. • PRP decreased MCP-1 level, caspase3 and α- SMA expression. • PRP improved redox status, mitochondrial function and increased renal cAMP, beclin1 and HGF levels • PRP has a reno-protective effect via cellular and molecular mechanisms. Abstract Chronic kidney diseases occur as result of exposure to wide range of deleterious agents as environmental pollutants, toxins and drug. Currently, there is no effective protective therapy against renal damage, fibrosis and its sequel of end stage renal disease. Platelet-rich plasma (PRP) has a progressively gained consideration in wound healing, repair/regeneration of damaged tissues and conservation of organ function. However, its impact on thioacetamide (TAA) induced chronic renal damage has not been elucidated yet. So, the present study was carried out to evaluate the possible protective and regenerative effect of PRP against TAA induced renal damage and their potential underlying mechanism. PRP treatment improved redox state, renal function disturbed histologicl features; decreased monocyte chemo-attractant protein-1 (MCP-1) level; increased Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) marker of mitochondrial biogenesis and metabolism; cyclic adenosine monophosphate (cAMP); hepatocyte growth factor (HGF) and autophagy protein beclin-1 level. In addition, PRP treatment decreased apoptosis and fibrosis as evidenced by decreased active caspase3 and α-SMA expression and immunoreactivity, respectively. In conclusion, PRP could potentially protect against TTA-induced chronic kidney damage by alleviating oxidative stress, improving, mitochondrial biogenesis, autophagy, disruption of the inflammatory, apoptotic and fibrotic response induced by TTA. [ABSTRACT FROM AUTHOR]

Problem Cholestasis can cause translocation of gut bacteria, and endotoxemia, and systemic inflammation. Now, little is known about the effects of cholestasis on the testicular inflammation and autophagy. Methods A rat biliary cholestasis model caused by common bile duct ligation ( CBDL), together with biliary decompression (choledochoduodenostomy), was used. Results The magnitude of MCP-1 expression and CD68+ macrophage infiltration within testes was progressively up-regulated in rats along with increasing duration of CBDL and was maintained at relatively high level in rats with biliary decompression. The large up-regulation of testicular ATG-12, LC3II, and autophagic vacuoles was found with the extending duration of CBDL and kept at 5 weeks following biliary decompression. The autophagic contents were a large accumulation of mitophagy in testes in rats with CBDL, and cytosol components in rats with biliary decompression. Conclusion Secondary biliary cholestasis can promote inflammatory reaction and the activation of mitophagy and autophagy in testes. [ABSTRACT FROM AUTHOR]

Background Inflammation plays a critical role in cancer progression, and our data suggested that ethanol ( Et OH) could promote the progression of breast cancer via increased monocyte chemo-attractant protein-1 ( MCP-1). Thus, we investigated the effects of Et OH on lung cancer growth and metastasis to explore whether immunosuppression had a role. Methods C57 BL/6 mice ( n = 10) implanted with Lewis lung cancer ( LLC) cells were used to model physiologically relevant Et OH intake on tumor growth and inflammation after macrophage polarization. Tumors were isolated and measured, and MCP-1 expression was measured via immunohistochemistry and Western blot. Recruitment of macrophages using CD11b and F4/80 antibodies was detected with immunohistochemistry and flow cytometry. Changes in arginase I and inducible nitric oxide synthase (iNOS) expression were measured with immunofluorescent microscopy. Et OH's effect on in vitro tumor angiogenesis was evaluated in culture, and the tumor microvessel density was assessed with CD31 immunohistochemistry. Matrix metalloproteinase 9 and interleukin 10 expressions were measured by Western blot, ELISA, and immunohistochemistry. Finally, we treated a macrophage cell line RAW264.7 with Et OH and measured changes in arginase I and i NOS expression. Results With Et OH exposure, macrophage density was positively correlated with MCP-1 expression. Macrophages infiltrated the tumor site, becoming tumor-associated macrophages that polarized to M2 phenotypes ( ArgIhigh/i NOSlow) after Et OH treatment. Cancerous cells interacted with immune cells, especially M2 macrophages, and promoted tumor angiogenesis, progression, and invasiveness. RAW264.7 cells stimulated with Et OH expressed more arginase I and less i NOS than controls. These results agreed with the features of M2 phenotype macrophages ( ArgIhigh/i NOSlow). Conclusions Data show that Et OH induced M2 phenotype macrophages, suggesting that progression and metastasis of LLC may be mediated by recruitment of M2 macrophages, especially under the influence of Et OH. [ABSTRACT FROM AUTHOR]

Pioglitazone increases renal tubular cell albumin uptake but limits proinflammatory and fibrotic responses. Background. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists, which are known to be critical factors in lipid metabolism, have also been reported to reduce proteinuria. The mechanism and its relevance to progressive nephropathy have not been determined. The aims of this study were to assess the direct effects of a PPARγ agonist on tubular cell albumin uptake, proinflammatory and profibrotic markers of renal pathology, using an opossum kidney model of proximal tubular cells. Methods. Cells were exposed to pioglitazone (10 μmol/L) in the presence and absence of low-density lipoprotein (LDL) 100 μg/mL ± exposure to albumin 1 mg/mL. Results were expressed relative to control (5 mmol/L glucose) conditions. Results. Pioglitazone caused a dose-dependent increase in tubular cell albumin uptake ( P < 0.0001). Despite the increase in albumin reabsorption, no concurrent increase in inflammatory or profibrotic markers were observed. Exposure to LDL increased monocyte chemoattractant protein-1 (MCP-1) ( P < 0.05) and transforming growth factor-β1 (TGF-β1) ( P < 0.05) production, which were reversed in the presence of pioglitazone. LDL induced increases in MCP-1 and TGF-β1 were independent of nuclear factor-κB (NF-κB) transcriptional activity. In contrast, tubular exposure to albumin increased tubular protein uptake, in parallel with an increase in MCP-1 ( P= 0.05), TGF-β1 ( P < 0.02) and NF-κB transcriptional activity ( P < 0.05), which were unaffected by concurrent exposure to pioglitazone. Conclusion. These findings suggest that dyslipidemia potentiates renal pathology through mechanisms that may be modified by PPARγ activation independent of NF-κB transcriptional activity. In contrast, tubular exposure to protein induces renal damage through NF-κB–dependent mechanisms that are unaffected by PPARγ activation. [ABSTRACT FROM AUTHOR]

Examines whether the chemokine monocyte chemo-attractant protein-1 (MCP-1) is produced locally in patients with bladder cancer and analyzes a possible correlation between tumor stage, grade and metastatic spread, and the urinary and systemic levels of MCP-1. Characteristics and functions of MCP-1; Potential role of MCP-1 in the recruitment of circulating monocytes to the bladder tumor site.

Diabetic retinopathy, a severe complication of diabetes, is the leading cause of blindness in the developed world. This study investigated the effects of quercetin on levels of monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in serum of rats with diabetic retinopathy, and explored the functional mechanisms of quercetin in the treatment of diabetic retinopathy. Twenty rats with induced diabetes were divided into a model group and a quercetin group, with 10 rats in each group. Ten healthy rats were also included to serve as a control group. Rats in the quercetin group were treated with an intragastric injection of quercetin (150 mg/kg), while the same amount of sodium carboxymethyl cellulose (CMCNa) was used for rats in the model group and the control group. The treatment was performed once per day and blood glucose was measured in each group at 0, 10 and 20 weeks after the first treatment. Blood glucose tests showed that quercetin did not reduce blood glucose in rats with diabetes. However, pathological examination showed that quercetin could relieve pathological changes caused by diabetes, such as retinal edema and vacuoles. ELISA results showed that, compared with the control group, levels of MCP-1, MMP-9 and VEGF in the model group were significantly increased (P<0.01). No significant difference in serum MCP-1 content was found between the model group and the quercetin group, but levels of MMP-9 and VEGF were significantly decreased in the quercetin group (P<0.01). Results of RT-PCR and western blot analysis showed that, compared with the control group, levels of MCP-1, MMP-9 and VEGF mRNA and protein in the retinal tissue of rats in the model group were significantly increased (P<0.01). No significant differences in expression levels of MCP-1 mRNA and protein were found between the model group and the quercetin group, but levels of MMP-9 and VEGF mRNA and protein were significantly decreased in the quercetin group (P<0.01). Quercetin has a certain therapeutic effect on rats with diabetic retinopathy and its effect may be achieved by reducing the expression of MMP-9 and VEGF, but not the inflammatory mediator, MCP-1.

Objectives: There is mounting evidence that inflammatory processes play a key role in emotional as well as cognitive dysfunctions. In this context, research employing magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MR spectroscopy) suggests a possible link between structural/functional anomalies in the brain and an increase of circulating inflammation markers. The present paper reviews this research, with particular focus on major depressive disorder (MDD), cognitive impairment in older adults, Alzheimer's disease (AD) and schizophrenia., Results: In MDD, cognitive impairment and AD, inflammatory processes have been found to be associated with both structural and functional anomalies, perhaps under the influence of environmental stress. Not enough research can suggest similar considerations in schizophrenia, although studies in mice and non-human primates support the belief that inflammatory responses generated during pregnancy can affect brain development and contribute to the etiology of schizophrenia., Conclusions: The present review suggests a link between inflammatory processes and MRI detected anomalies in the brain of individuals with MDD, older adults with cognitive impairment as well as of individuals with AD and schizophrenia., (Copyright © 2013 Elsevier Inc. All rights reserved.)