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MCP-1 Production (mcp-1 + production)
Selected AbstractsRelease of monocyte chemoattractant protein (MCP)-1 by a human alveolar epithelial cell line in response to Mycobacterium aviumFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2000Savita P. Rao Abstract Clinical strains of Mycobacterium avium isolated from patients with acquired immunodeficiency syndrome, but not a non-clinical laboratory strain (ATCC 25291), were found to stimulate the human alveolar epithelial cell line A549, to produce monocyte chemoattractant protein (MCP)-1. A549 cells were also found to produce elevated levels of MCP-1 in response to sonicates of the clinical strains of M. avium, and surprisingly, the non-clinical strain as well. However, sonic extracts of the clinical strains were found to induce significantly higher levels of MCP-1 production compared to extracts of the non-clinical strain (P<0.001). These data suggest the existence of strain-related differences in antigen expression by M. avium. The clinical and non-clinical strains of M. avium were found to attach and invade, but not replicate in A549 cells indicating that MCP-1 production by A549 cells does require the presence of viable, replicating organisms. Activation of alveolar epithelial cells by exposure to M. avium resulting in the production of chemokines which recruit inflammatory cells to the site of infection may be an important regulatory pathway for the activation of pulmonary host defense. [source] Monocyte chemoattractant protein-1 (MCP-1) produced via NF-,B signaling pathway mediates migration of amoeboid microglia in the periventricular white matter in hypoxic neonatal ratsGLIA, Issue 6 2009Y. Y. Deng Abstract Monocyte chemoattractant protein-1 (MCP-1), a member of ,-chemokine subfamily, regulates the migration of microglia, monocytes, and lymphocytes to the inflammatory site in the central nervous system. We sought to determine if amoeboid microglial cells (AMC) produce MCP-1 that may be linked to migration of AMC in the corpus callosum periventricular white matter in hypoxic neonatal rats. A striking feature in 1-day-old rats subjected to hypoxia was a marked increase in cell numbers of AMC and immunoexpression of MCP-1 and its receptor (CCR2). By BrdU immunostaining, there was no significant change in the proliferation rate of AMC after hypoxic exposure when compared with the corresponding control rats. When injected intracerebrally into the corpus callosum of 7-day-old postnatal rats, MCP-1 induced the chemotactic migration of AMC to the injection site. In primary microglial cell culture subjected to hypoxia, there was a significant increase in MCP-1 release involving NF-,B signaling pathway. In in vitro chemotaxis assay, the medium derived from hypoxia-treated microglial cultures attracted more migratory microglial cells than that from the control microglial culture. The present results suggest that following a hypoxic insult, AMC in the neonatal rats increase MCP-1 production via NF-,B signaling pathway. This induces the migration and accumulation of AMC from the neighboring areas to the periventricular white matter (PWM). It is concluded that the preponderance and active migration of AMC, as well as them being the main cellular source of MCP-1, may offer an explanation for the PWM being susceptible to hypoxic damage in neonatal brain. © 2008 Wiley-Liss, Inc. [source] HIV-1 Tat and opiate-induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP-1 and alternative chemokinesGLIA, Issue 2 2006Nazira El-Hage Abstract Opiates exacerbate human immunodeficiency virus type 1 (HIV-1) Tat1-72 -induced release of key proinflammatory cytokines by astrocytes, which may accelerate HIV neuropathogenesis in opiate abusers. The release of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), in particular, is potentiated by opiate,HIV Tat interactions in vitro. Although MCP-1 draws monocytes/macrophages to sites of CNS infection, and activated monocytes/microglia release factors that can damage bystander neurons, the role of MCP-1 in neuro-acquired immunodeficiency syndrome (neuroAIDS) progression in opiate abusers, or nonabusers, is uncertain. Using a chemotaxis assay, N9 microglial cell migration was found to be significantly greater in conditioned medium from mouse striatal astrocytes exposed to morphine and/or Tat1-72 than in vehicle-, ,-opioid receptor (MOR) antagonist-, or inactive, mutant Tat,31-61 -treated controls. Conditioned medium from astrocytes treated with morphine and Tat caused the greatest increase in motility. The response was attenuated using conditioned medium immunoneutralized with MCP-1 antibodies, or medium from MCP-1,/, astrocytes. In the presence of morphine (time-release, subcutaneous implant), intrastriatal Tat increased the proportion of neural cells that were astroglia and F4/80+ macrophages at 7 days post-injection. This was not seen after treatment with Tat alone, or with morphine plus inactive Tat,31-61 or naltrexone. Glia displayed increased MOR and MCP-1 immunoreactivity after morphine and/or Tat exposure. The findings indicate that MCP-1 underlies most of the response of microglia, suggesting that one way in which opiates exacerbate neuroAIDS is by increasing astroglial-derived proinflammatory chemokines at focal sites of CNS infection and promoting macrophage entry and local microglial activation. Importantly, increased glial expression of MOR can trigger an opiate-driven amplification/positive feedback of MCP-1 production and inflammation. © 2005 Wiley-Liss, Inc. [source] Regulation of MCP-1 production in brain by stress and noradrenaline-modulating drugsJOURNAL OF NEUROCHEMISTRY, Issue 2 2010Jose L. M. Madrigal J. Neurochem. (2010) 113, 543,551. Abstract While it is accepted that noradrenaline (NA) reduction in brain contributes to the progression of certain neurodegenerative diseases, the mechanisms through which NA exerts its protective actions are not well known. We previously reported that NA induced production of monocyte chemoattractant protein (MCP-1/CCL2) in cultured astrocytes mediated some of the neuroprotective actions of NA. We have now examined the regulation of MCP-1 production in vivo. Treatment of mice with the NA precursor l -threo-3,4-dihydroxyphenylserine induced the production of MCP-1 in astrocytes. In contrast, exposure to stress (a process known to elevate brain NA levels) produced only a moderate increase of MCP-1 because of the inhibitory activity of glucocorticoids released during the stress response. Similarly, corticosterone treatment of astrocytes caused a reduction of constitutive as well as the NA-induced MCP-1 production. When stressed rats had the production of glucocorticoids blocked by the selective inhibitor metyrapone, a large increase of MCP-1 concentration was observed in cortex, whereas propranolol (a beta adrenergic receptor blocker) avoided modifications of MCP-1 after stress. Desipramine (an inhibitor of NA reuptake) also caused an increase of MCP-1 in cortex. These data suggest that some phenomena caused by the alteration of NA or glucocorticoids could be mediated by MCP-1. [source] Dexamethasone suppresses monocyte chemoattractant protein-1 production via mitogen activated protein kinase phosphatase-1 dependent inhibition of Jun N-terminal kinase and p38 mitogen-activated protein kinase in activated rat microgliaJOURNAL OF NEUROCHEMISTRY, Issue 3 2007Yan Zhou Abstract Microglial cells release monocyte chemoattractant protein-1 (MCP-1) which amplifies the inflammation process by promoting recruitment of macrophages and microglia to inflammatory sites in several neurological diseases. In the present study, dexamethasone (Dex), an anti-inflammatory and immunosuppressive drug has been shown to suppress the mRNA and protein expression of MCP-1 in activated microglia resulting in inhibition of microglial migration. This has been further confirmed by the chemotaxis assay which showed that Dex or MCP-1 neutralization with its antibody inhibits the microglial recruitment towards the conditioned medium of lipopolysaccharide (LPS)-treated microglial culture. This study also revealed that the down-regulation of the MCP-1 mRNA expression by Dex in activated microglial cells was mediated via mitogen-activated protein kinase (MAPK) pathways. It has been demonstrated that Dex inhibited the phosphorylation of Jun N-terminal kinase (JNK) and p38 MAP kinases as well as c-jun, the JNK substrate in microglia treated with LPS. The involvement of JNK and p38 MAPK pathways in induction of MCP-1 production in activated microglial cells was confirmed as there was an attenuation of MCP-1 protein release when microglial cells were treated with inhibitors of JNK and p38. In addition, Dex induced the expression of MAP kinase phosphatase-1 (MKP-1), the negative regulator of JNK and p38 MAP kinases in microglial cells exposed to LPS. Blockade of MKP-1 expression by triptolide enhanced the phosphorylation of JNK and p38 MAPK pathways and the mRNA expression of MCP-1 in activated microglial cells treated with Dex. In summary, Dex inhibits the MCP-1 production and subsequent microglial cells migration to the inflammatory site by regulating MKP-1 expression and the p38 and JNK MAPK pathways. This study reveals that the MKP-1 and MCP-1 as novel mediators of biological effects of Dex may help developing better therapeutic strategies for the treatment of patients with neuroinflammatory diseases. [source] Neutralizing antibody against severe acute respiratory syndrome (SARS)-coronavirus spike is highly effective for the protection of mice in the murine SARS modelMICROBIOLOGY AND IMMUNOLOGY, Issue 2 2009Koji Ishii ABSTRACT We evaluated the efficacy of three SARS vaccine candidates in a murine SARS model utilizing low-virulence Pp and SARS-CoV coinfection. Vaccinated mice were protected from severe respiratory disease in parallel with a low virus titer in the lungs and a high neutralizing antibody titer in the plasma. Importantly, the administration of spike protein-specific neutralizing monoclonal antibody protected mice from the disease, indicating that the neutralization is sufficient for protection. Moreover, a high level of IL-6 and MCP-1 production, but not other 18 cytokines tested, on days 2 and 3 after SARS-CoV infection was closely linked to the virus replication and disease severity, suggesting the importance of these cytokines in the lung pathogenicity of SARS-CoV infection. [source] Reduced apoptosis in BALB/c mice infected with Heligmosomoides polygyrusPARASITE IMMUNOLOGY, Issue 6 2007M. DOLIGALSKA SUMMARY We evaluated levels of apoptosis and the immune response ex vivo in BALB/c mice infected with Heligmosomoides polygyrus. Cell proliferation, apoptosis and cytokine production were measured in mesenteric lymph nodes (MLN) without exposure to H. polygyrus antigens in culture. The inhibited apoptosis and cytokine production reported might reflect a state of cell hyporesponsiveness in the prepatent phase of infection. These changes were accompanied by changes in the percentage of CD4+ cells in MLN and popliteal lymph nodes (PLN). The prolonged reduction in apoptosis coexisted with induced cell proliferation, elevated TNF-,, IL-12p70, IFN-,, IL-6, IL-10 and TGF-, synthesis, but lowered IL-4 and IL-2 levels. In the chronic phase of infection an increasing production of IFN-,, monocyte chemotactic protein-1 (MCP-1), IL-10 and TGF-, with decreasing concentrations of other cytokines resulted in restored apoptosis. The cytokine response in serum showed moderate production of TNF-,, temporary involvement of IL-12p70, induction of IFN-, and IL-10 synthesis, as well as growing IL-6 and MCP-1 production. It is suggested that a synchronized synthesis of distinct cytokines is accompanied by different levels of inhibited apoptosis during the prepatent and chronic phases of H. polygyrus infection in BALB/c mice. We suggest that immunosuppression provoked by the nematode is not the outcome of parasite-induced apoptosis, but rather results from a hyporesponsiveness experienced by cells during H. polygyrus infection. [source] Atorvastatin Decreases C-Reactive Protein-Induced Inflammatory Response in Pulmonary Artery Smooth Muscle Cells by Inhibiting Nuclear Factor-,B PathwayCARDIOVASCULAR THERAPEUTICS, Issue 1 2010Jie Li C-reactive protein (CRP) is well-known inflammatory marker, and recognized as a risk predictor of pulmonary arterial diseases. Although statins have a beneficial effect in animal models and patients with pulmonary arterial hypertension (PAH), the underlying mechanisms of their actions have less been investigated. The aims of this study was to examined the effects of CRP on expressions of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), and the possible mechanisms of atorvastatin on CRP-induced IL-6 and MCP-1 production in cultured human pulmonary artery smooth muscle cells (PASMCs). In a preliminary study, the human PASMCs were stimulated by a variety of concentrations of CRP (5,200 ,g/mL) at different time points (0, 3, 6, 9, 12, 18 and 24 h) for the purpose of determining the dose- and time-dependent effects of CRP on inflammatory response of the cells. Then, the cells were pre-incubated for 2 h with atorvastatin (0.1,10 ,mol/L) in the presence of CRP. The supernatant levels of both IL-6 and MCP-1 secretion were examined by ELISA. The cellular mRNA expressions of IL-6 and MCP-1 and nuclear factor-,B (NF-,B) activity were determined by real-time reverse transcription and polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA), respectively. CRP resulted in elevated IL-6 and MCP-1 secretion and mRNA expression in a dose- and time-dependent manner. In addition, CRP also significantly activated the NF-,B pathway. Preincubation with 0.1,10 ,mol/L of atorvastatin significantly decreased the secretions of IL-6 and MCP-1 induced by CRP. Moreover, 10 ,mol/L of atorvastatin completely abrogated CRP-induced increase in IL-6 and MCP-1 by attenuating the activation of NF-,B. The present study demonstrated that inhibiting effect of atorvastatin on CRP-induced inflammatory response in cultured PASMCs was associated with NF-,B pathway. This pathway might represent a promising target for controlling CRP-induced inflammatory response in pulmonary arterial diseases. [source] | |||||||||||||