Modulation of morphological changes of microglia and neuroprotection by monocyte chemoattractant protein-1 in experimental glaucoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Chiu K
PROVIDER: S-EPMC4003260 | biostudies-other | 2010 Jan
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Microglia dynamically adapt their morphology and function during increasing age. However, the mechanisms behind these changes are to date poorly understood. Glucocorticoids (GCs) are long known and utilized for their immunomodulatory actions and endogenous GC levels are described to alter with advancing age. We here tested the hypothesis that age-associated elevations in GC levels implicate microglia function and morphology. Our data indicate a decrease in microglial complexity and a concomitant increase in GC levels during aging. Interestingly, enhancing GC levels in young mice enhanced microglial ramifications, while the knockdown of the glucocorticoid receptor expression in old mice aggravated age-associated microglial amoebification. These data suggest that GCs increase ramification of hippocampal microglia and may modulate age-associated changes in microglial morphology.
| S-EPMC6052476 | biostudies-literature
Project description:This study identifies monocyte chemoattractant protein 1 (MCP-1) as an insulin-responsive gene. It also shows that insulin induces substantial expression and secretion of MCP-1 both in vitro in insulin-resistant (IR) 3T3-L1 adipocytes and in vivo in IR obese mice (ob/ob). Thus, MCP-1 resembles other previously described genes (e.g., PAI-1 and SREBP-1c) that remain sensitive to insulin in IR states. The hyperinsulinemia that frequently accompanies obesity and insulin resistance may therefore contribute to the altered expression of these and other genes in insulin target tissues. In vivo studies also demonstrate that MCP-1 is overexpressed in obese mice compared with their lean controls, and that white adipose tissue is a major source of MCP-1. The elevated MCP-1 may alter adipocyte function because addition of MCP-1 to differentiated adipocytes in vitro decreases insulin-stimulated glucose uptake and the expression of several adipogenic genes (LpL, adipsin, GLUT-4, aP2, beta3-adrenergic receptor, and peroxisome proliferator-activated receptor gamma). These results suggest that elevated MCP-1 may induce adipocyte dedifferentiation and contribute to pathologies associated with hyperinsulinemia and obesity, including type II diabetes.
| S-EPMC165864 | biostudies-literature
Project description:The data presented in this article are related to the research article entitled "Elevated levels of monocyte chemoattractant protein-1 in the aqueous humor after phacoemulsification" (M. Kawai, T. Inoue, M. Inatani, N. Tsuboi, K. Shobayashi, A. Matsukawa, A. Yoshida, H, 2012) [1]. The mean (±SE) aqueous MCP-1 levels (pg/ml) were 31.2±12.5, 1931.2±910.7, 2172.2±1015.7, 3315.4 ±1535.8, 3015.9 ±914.4, 2709.0 ±738.7, 72.8 ±26.9, and 207.1±62.9 at 0, 3, 6, 12, 24, 48, 168, and 720 h after phacoemulsification, respectively. The immunohistochemical analysis showed a number of MCP-1 positive inflammatory cells in the anterior chamber and conjunctiva. There were some MCP-1 positive cells in the corneal endothelium.
| S-EPMC5114530 | biostudies-other
Project description:Photoreceptor apoptosis is a major cause of visual loss in retinal detachment (RD) and several other visual disorders, but the underlying mechanisms remain elusive. Recently, increased expression of monocyte chemoattractant protein 1 (MCP-1) was reported in vitreous humor samples of patients with RD and diabetic retinopathy as well as in the brain tissues of patients with neurodegenerative diseases, including Alzheimer's disease and multiple sclerosis. Here we report that MCP-1 plays a critical role in mediating photoreceptor apoptosis in an experimental model of RD. RD led to increased MCP-1 expression in the Müller glia and increased CD11b+ macrophage/microglia in the detached retina. An MCP-1 blocking antibody greatly reduced macrophage/microglia infiltration and RD-induced photoreceptor apoptosis. Confirming these results, MCP-1 gene-deficient mice showed significantly reduced macrophage/microglia infiltration after RD and very little photoreceptor apoptosis. In primary retinal mixed cultures, MCP-1 was cytotoxic for recoverin+ photoreceptors, and this toxicity was eliminated through immunodepleting macrophage/microglia from the culture. In vivo, deletion of the gene encoding CD11b/CD18 nearly eliminated macrophage/microglia infiltration to the retina after RD and the loss of photoreceptors. Thus, MCP-1 expression and subsequent macrophage/microglia infiltration and activation are critical for RD-induced photoreceptor apoptosis. This pathway may be an important therapeutic target for preventing photoreceptor apoptosis in RD and other CNS diseases that share a common etiology.
| S-EPMC1892947 | biostudies-literature
Project description:Objective The expression level of monocyte chemoattractant protein-1 (MCP-1) is increased in atherosclerotic regions, inducing monocyte migration to the blood vessel wall. Although the serum MCP-1 concentration is higher in patients with than without cardiovascular disease, the precise correlations between the serum MCP-1 concentration and factors associated with smoking and atherosclerosis are unknown. Methods The serum MCP-1 concentration was measured using an enzyme-linked immunosorbent assay in 207 consecutive smokers who visited our smoking cessation clinic. Results Sex-adjusted analysis of smokers revealed that the MCP-1 concentration was positively correlated with age ( ??=?0.311), smoking duration ( ??=?0.342), systolic blood pressure ( ??=?0.225), and diastolic blood pressure ( ??=?0.137) but not with the body mass index. Multivariate regression analysis showed that smoking duration and systolic blood pressure were independent determinants of the MCP-1 concentration. Conclusions The MCP-1 concentration was positively correlated with blood pressure among smokers. Long-term smokers with high blood pressure may be more susceptible to plaque rupture at atherosclerotic lesion sites.
| S-EPMC5972233 | biostudies-literature
Project description:In the present article we describe the gas-phase dissociation behavior of the dimeric form of monocyte chemoattractant protein-1 (MCP-1) using quadrupole-traveling wave ion mobility-time of flight mass spectrometry (q-TWIMS-TOF MS) (Waters Synapt™). Through investigation of the 9(+) charge state of the dimer, we were able to monitor dissociation product ion (monomer) formation as a function of activation energy. Using ion mobility, we were able to observe precursor ion structural changes occurring throughout the activation process. Arrival time distributions (ATDs) for the 5(+) monomeric MCP-1 product ions, derived from the gas-phase dissociation of the 9(+) dimer, were then compared with ATDs obtained for the 5(+) MCP-1 monomer isolated directly from solution. The results show that the dissociated monomer is as compact as the monomer arising from solution, regardless of the trap collision energy (CE) used in the dissociation. The solution-derived monomer, when collisionally activated, also resists significant unfolding within measure. Finally, we compared the collisional activation data for the MCP-1 dimer with an MCP-1 dimer non-covalently bound to a single molecule of the semi-synthetic glycosaminoglycan (GAG) analog Arixtra™; the latter a therapeutic anti-thrombin III-activating pentasaccharide. We observed that while dimeric MCP-1 dissociated at relatively low trap CEs, the Arixtra-bound dimer required much higher energies, which also induced covalent bond cleavage in the bound Arixtra molecule. Both the free and Arixtra-bound dimers became less compact and exhibited longer arrival times with increasing trap CEs, albeit the Arixtra-bound complex at slightly higher energies. That both dimers shifted to longer arrival times with increasing activation energy, while the dissociated MCP-1 monomers remained compact, suggests that the longer arrival times of the Arixtra-free and Arixtra-bound dimers may represent a partial breach of non-covalent interactions between the associated MCP-1 monomers, rather than extensive unfolding of individual subunits. The fact that Arixtra preferentially binds MCP-1 dimers and prevents dimer dissociation at comparable activation energies to the Arixtra-free dimer, may suggest that the drug interacts across the two monomers, thereby inhibiting their dissociation.
| S-EPMC2769070 | biostudies-literature
Project description:PurposeTo compare posterior corneal morphology between older treated and younger untreated children with primary congenital glaucoma (PCG) using anterior segment optical coherence tomography (ASOCT) and intraoperative OCT (iOCT), respectively.MethodsIn this comparative study, ASOCT of older PCG children were compared with iOCT of younger untreated PCG patients. Differences between the two groups with respect to posterior corneal morphology were studied.ResultsObserved morphological patterns within posterior cornea in older treated (age: 72-300 months) children (87 eyes) included Descemet's membrane (DM) excrescences (70%), thickened DM (35%), intracameral twin protuberances (92%), and DM detachment (26%). Changes within pre-Descemet's layer (PDL) (28%) included thickening, breaks, and detachments. Extent of Haab's striae was associated with thickness of DM/PDL complex (P = 0.008) when analyzed in the treated group. In contrast, in the untreated group (n = 53 eyes, age 1-63 months), posterior corneal changes were limited to diffuse hyper-reflectivity of the DM/PDL complex, with absence of DM tears.ConclusionPosterior cornea thickens and Haab's striae become more circumscribed in eyes of older treated children compared to untreated PCG eyes, probably reflecting a healing response of posterior cornea over time.
| S-EPMC9426191 | biostudies-literature
Project description:Parkinson's disease (PD) and multiple system atrophy (MSA) have overlapping symptoms, challenging a correct early diagnosis. Prognostic information is needed to predict disease progression and provide appropriate counseling. Neuroinflammation plays a role in the pathology of both disorders, as shown in genetic and postmortem tissue studies. Monocyte chemoattractant protein 1 (MCP-1) and neuroleukin (NLK) are two inflammatory proteins with potential to serve as biomarkers of the neuroinflammatory process. Here, we aimed to study the biomarker potential of both MCP-1 and NLK protein levels in cerebrospinal fluid (CSF) from a longitudinal cohort study (Radboudumc, Nijmegen, The Netherlands), consisting of PD patients (n = 46), MSA patients (n = 17) and control subjects (n = 52) using ELISA. We also correlated MCP-1 and NLK levels in CSF to several parameters of disease. We showed that MCP-1 levels in CSF positively correlate with PD progression (ρ = 0.363; p = 0.017) but could not differentiate between PD, MSA, and controls. NLK levels in CSF neither differentiated between PD, MSA, and controls, nor correlated with disease progression. Our results indicate that MCP-1 levels in CSF cannot distinguish between PD, MSA, and controls but correlate with disease progression in PD patients, suggesting that neuroinflammation is associated with clinical progression in PD. The correlation with disease progression was only moderate, so MCP-1 levels in CSF should be included in a larger battery of prognostic biomarkers that also tackle different pathophysiological processes.
| S-EPMC7471278 | biostudies-literature
Project description:Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in various inflammatory diseases. To reveal the impact of MCP-1 during diseases and to develop anti-inflammatory agents, we establish a transgenic mouse line. The firefly luciferase gene is incorporated into the mouse genome and driven by the endogenous MCP-1 promoter. A bioluminescence photographing system is applied to monitor luciferase levels in live mice during inflammation, including lipopolysaccharide-induced sepsis, concanavalin A-induced T cell-dependent liver injury, CCl 4-induced acute hepatitis, and liver fibrosis. The results demonstrate that the luciferase signal induced in inflammatory processes is correlated with endogenous MCP-1 expression in mice. Furthermore, the expressions of MCP-1 and the luciferase gene are dramatically inhibited by administration of the anti-inflammatory drug dexamethasone in a septicemia model. Our results suggest that the transgenic MCP-1-Luc mouse is a useful model to study MCP-1 expression in inflammation and disease and to evaluate the efficiency of anti-inflammatory drugs in vivo.
| S-EPMC9828394 | biostudies-literature
Project description:BackgroundNeurodegenerative disorders such Alzheimer's disease (AD) are often characterized by senile plaques and neurofibrillary tangle. In addition, reactive astrogliosis, microglia activation and a chronic inflammation are found in AD brain. Activated microglia has been reported to express a large number of beta chemokines including monocyte chemoattractant protein-1 (MCP-1). The potential role of MCP-1 in AD pathogenesis is supported by the over expression of MCP-1 associated with an increase of amyloid deposition in transgenic mice. MCP-1 protein may be regulated by a single nucleotide polymorphism (SNP) occurring at position -2518 of the MCP-1 gene promoter. In this paper we correlated the A-2518G MCP-1 SNP distribution in three different populations: AD, control and MCI (mild cognitive impairment) population to evaluate whether this SNP might be a risk factor for AD or for MCI-AD conversion. MCP-1 plasma levels were also measured and correlated to the cognitive impairment (CIND) and AD risk.ResultsNo differences in genotype distribution and allele frequencies of A-2518G MCP-1 SNP among AD patients, MCI subjects and controls were observed even after APOEe4 variation adjustment with logistic regression. However in MCI subjects, followed up for two years, this SNP appears to influence the progression of the disease; being the G allele slightly more frequent in MCI patients that developed AD. MCP-1 plasma levels were different among CIND (cognitive impairment but no dementia), AD and controls. The MCP-1 A-2518G promoter polymorphism did not affect MCP-1 plasma levels within the three populations.ConclusionsMCP-1 G allele did not affect the risk of AD, but slightly influenced MCI conversion to AD and MCP-1 plasma levels were increased in subjects with preclinical AD.
| S-EPMC3610278 | biostudies-literature