MCP-1-stimulated monocyte attachment to laminin is mediated by beta 2-integrins

1994 ◽  
Vol 267 (4) ◽  
pp. C1112-C1118 ◽  
Author(s):  
Y. Jiang ◽  
J. F. Zhu ◽  
F. W. Luscinskas ◽  
D. T. Graves
Keyword(s):  
Collagen Iv ◽  
Matrix Proteins ◽  
Time Dependent ◽  
Integrin Subunit ◽  
Dependent Manner ◽  
Monocyte Adhesion ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Beta 1 Integrin ◽  
Beta 2

Migration of monocytes to sites of inflammation involves a series of attachments and detachments to extracellular matrix proteins. We examined the capacity of a chemokine, monocyte chemoattractant protein-1 (MCP-1), to regulate attachment of human monocytes to laminin, collagen I, collagen IV, or fibronectin. MCP-1 increased monocyte attachment to laminin in a dose- and time-dependent manner and stimulated a lesser increase to the other matrix proteins. Function-blocking monoclonal antibodies (MAbs) to the integrin beta 2-subunit (CD18), including Fab' fragments and alpha M (CD11b) blocked > 70% of attachment, whereas MAbs to the beta 1-integrin subunit reduced attachment by < 30%. This suggests that the CD11b/CD18 integrin is the predominant molecule involved in adhesion of MCP-1-stimulated monocytes to laminin. The association of CD11b with F-actin illustrated by confocal microscopy further supports this concept. In contrast, when monocytes were stimulated with the beta 1-stimulatory MAb TS2/16, monocyte adhesion to laminin occurred through beta 1-integrins. Thus MCP-1 can stimulate monocyte attachment to laminin, and this process is mediated through beta 2-integrins, principally CD11b/CD18.

MCP-1-stimulated monocytes preferentially utilize beta 2-integrins to migrate on laminin and fibronectin

1995 ◽  
Vol 269 (1) ◽  
pp. C60-C68 ◽  
Author(s):  
T. W. Penberthy ◽  
Y. Jiang ◽  
F. W. Luscinskas ◽  
D. T. Graves
Keyword(s):  
Extracellular Matrix ◽  
Human Peripheral Blood ◽  
Neutrophil Migration ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Migration ◽  
Beta 2

Recruitment of monocytes to inflammatory sites involves a series of sequential attachments and detachments to extracellular matrix proteins in response to a chemoattractant gradient. In this study we compared the migration of human peripheral blood monocytes on different extracellular matrix proteins in response to monocyte chemoattractant protein-1 (MCP-1) and N-formylmethionyl-leucyl-phenylalanine. Monocytes migrated more effectively on laminin compared with other extracellular matrix proteins. In contrast, this preference was not observed with neutrophils, suggesting that the monocytes and neutrophils may have differences in their migration on extracellular matrix proteins. To study this further, function-blocking monoclonal antibodies were used to examine mechanistically whether beta 1- and beta 2-integrins were involved in monocyte migration on fibronectin or laminin in response to MCP-1. Monocyte migration on both laminin and fibronectin was blocked 100% (P < 0.05) by intact monoclonal antibody, F(ab') fragments, and F(ab')2 fragments to beta 2-integrins. We also determined that antibodies to beta 2-integrins block monocyte migration that has already been initiated. In contrast, antibody to the beta 1-integrins inhibited monocyte migration by approximately 40% (P < 0.05). Thus monocytes that express both beta 1- and beta 2-integrins require utilization of beta 2-integrins in migration on extracellular matrix proteins. The results also suggest that beta 1-integrins facilitate monocyte migration but that monocyte migration is not absolutely dependent on the interaction of beta 1-integrins with extracellular matrix proteins. In contrast, neutrophil migration is beta 2-integrin dependent and is not facilitated by beta 1-integrins.

Hyperoxia increases plasminogen activator activity of cultured endothelial cells

1992 ◽  
Vol 262 (1) ◽  
pp. L21-L31 ◽  
Author(s):  
P. G. Phillips ◽  
L. Birnby ◽  
L. A. Di Bernardo ◽  
T. J. Ryan ◽  
M. F. Tsan
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Collagen Iv ◽  
Matrix Proteins ◽  
Time Dependent ◽  
Focal Contact ◽  
Oxygen Exposure ◽  
Endothelial Monolayers ◽  
Cell Fractions

Confluent calf pulmonary artery endothelial monolayers exposed to 95% oxygen for 1, 2, or 3 days exhibit a time-dependent increase in adherence to substratum, which closely parallels changes in actin cytoarchitecture and the distribution of focal contact proteins vinculin and talin. Oxygen exposure also resulted in elevated plasminogen activator (PA) activity in conditioned media (CM) and in cytoskeletal protein- and focal contact protein-enriched fractions, with highest levels achieved in the latter two fractions at 48 h after oxygen exposure. PAs have been shown to participate in dismantling of extracellular matrix in a number of physiological and pathological situations. Immunocytochemical studies demonstrated extensive restructuring of matrix proteins collagen IV, laminin, and fibronectin, which correlated temporally with elevated PA levels. Further, when protease-containing cell fractions were used to study degradation of isolated matrices, those obtained from hyperoxia-exposed cells were substantially more active than those from normoxia-exposed cells. Our data suggest that hyperoxia-induced production of PA (and perhaps other proteases) may be partly responsible for degradation of the extracellular matrix of endothelial cells.

ER stress triggers MCP-1 expression through SET7/9-induced histone methylation in the kidneys of db/db mice

2014 ◽  
Vol 306 (8) ◽  
pp. F916-F925 ◽  
Author(s):  
Jigang Chen ◽  
Yanhong Guo ◽  
Wei Zeng ◽  
Li Huang ◽  
Qi Pang ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Er Stress ◽  
Regulatory Mechanism ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Reporter Assay ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Glucose Regulated Protein

Epigenetics plays a key role in the pathogenesis of diabetic nephropathy (DN), although the precise regulatory mechanism is still unclear. Here, we examined the role of endoplasmic reticulum (ER) stress in histone H3 lysine 4 (H3K4) methyltransferase SET7/9-induced monocyte chemoattractant protein-1 (MCP-1) expression in the kidneys of db/db mice. Our results indicate that the expression of MCP-1 significantly increased in the kidneys of db/db mice in a time-dependent manner. An increased chromatin mark associated with an active gene (H3K4me1) at MCP-1 promoters accompanied this change in expression. The expression of SET7/9 and the recruitment to these promoters were also elevated. SET7/9 gene silencing with small interfering (si) RNAs significantly attenuated the expression of H3K4me1 and MCP-1. Furthermore, expression of signaling regulator glucose-regulated protein 78 (GRP78), a monitor of ER stress, significantly increased in the kidneys of db/db mice. The expression of spliced X-box binding protein 1 (XBP1s), an ER stress-inducible transcription factor, and recruitment to the SET7/9 promoters were also increased. XBP1s gene silencing with siRNAs significantly attenuated the expression of SET7/9, H3K4me1, and MCP-1. The chaperone betaine not only effectively downregulated the GRP78 and XBP1s expression levels but also markedly decreased the SET7/9, H3K4me1, and MCP-1 levels. Luciferase reporter assay demonstrated that XBP1s participated in ER stress-induced SET7/9 transcription, Taken together, these results reveal that ER stress can trigger the expression of MCP-1, in part through the XBP1s-mediated induction of SET7/9.

HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by transmigration of monocytes

Blood ◽  
2001 ◽  
Vol 97 (2) ◽  
pp. 352-358 ◽  
Author(s):  
In-Woo Park ◽  
Jian-Feng Wang ◽  
Jerome E. Groopman
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Dependent Manner ◽  
Endothelial Monolayer ◽  
Monocyte Chemoattractant Protein 1 ◽  
Pkc Inhibitor ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Infected Cells ◽  
Hiv 1

Abstract The mechanism whereby HIV-infected cells transit from the bloodstream into tissues is not well defined. This phenomenon was addressed by studying the effects of HIV-1 Tat, a protein secreted by infected cells, on human lung microvascular endothelial cells (HMVEC-Ls). It was found that monocyte chemoattractant protein-1 (MCP-1) was released from HMVEC-Ls in a dose- and time-dependent manner after Tat treatment. MCP-1 is a potent β-chemokine that recruits monocytes and T cells and promotes cell adhesion and transmigration across an endothelial monolayer. It was also observed that MCP-1 and the culture medium from Tat-treated HMVEC-Ls were chemotactic for CD14+ monocytes from human peripheral blood and for THP-1, a promonocytic cell line used as a model system. To characterize the signaling pathways underlying the observed induction of MCP-1, HMVEC-Ls were treated with 2 different protein kinase inhibitors: PD98059, a MAP kinase inhibitor, and GF109203X, a protein kinase C (PKC) inhibitor. MCP-1 release was significantly reduced when PKC was inhibited, and slightly decreased when PI3 kinase was blocked; no effect on MCP-1 release was observed on MAP kinase inhibition. Similarly, transmigration of THP-1 cells was significantly impaired by the PKC inhibitor, but not by the other tested inhibitors. These data indicate that the HIV-1 Tat protein may act as a protocytokine by causing the release of MCP-1 from the endothelial monolayer, and thereby facilitating monocyte transmigration into tissues via a PKC signaling pathway.

Immuno-EM localization of the beta 1 integrin subunit in wet-cleaved fibronectin-adherent fibroblasts

1994 ◽  
Vol 107 (5) ◽  
pp. 1229-1239 ◽  
Author(s):  
A.M. Meijne ◽  
D.M. Casey ◽  
C.A. Feltkamp ◽  
E. Roos
Keyword(s):  
Plasma Membranes ◽  
Matrix Proteins ◽  
Integrin Subunit ◽  
Beta 1 Integrin ◽  
Coated Surface ◽  
20 Nm ◽  
Fibronectin Fibrils ◽  
Adhesion Plaque ◽  
Punctate Staining ◽  
Chicken Embryo Fibroblasts

Using immuno-EM, we have studied the distribution of the beta 1 integrin subunit in chicken embryo fibroblasts allowed to adhere and spread for 3 hours on a fibronectin-coated surface in serum-free medium. The cells were wet-cleaved, which removed most of the cell body, yielding ventral plasma membranes with little, and sometimes virtually no, associated cytoskeleton. The beta 1 integrin subunit was detected with antibodies against the cytoplasmic domain. In immune fluorescence, it colocalized with adhesion plaques, in a punctate staining pattern, and often seemed to be at the periphery of the plaque. By immuno-EM, beta 1 was in fact found in discrete clusters, not throughout the plaque. In deep-cleaved cells from which virtually all cytoskeleton was removed, clusters could often be seen to be located on fibronectin fibrils. Furthermore, beta 1 was present in clusters at the cell margins, and isolated or in small groups at the very edge of the cell. When fibronectin synthesis, and consequently fibril formation, was inhibited by cycloheximide, large adhesion plaque-like structures were formed at the cell margin. This phenotype was reversed by addition of soluble fibronectin, which was incorporated into fibrils. As in normal plaques, talin and vinculin were present, the plasma membrane was very close (10-20 nm) to the substratum and the fibronectin layer underneath was removed. These plaques did contain beta 1 integrins but they were not in clusters. These observations indicate that the talin-vinculin network of an adhesion plaque is normally anchored to the substratum at discrete beta 1 integrin clusters that may be located on fibronectin fibrils, and that elsewhere the plaque is not necessarily attached to the substratum by interaction of integrins with matrix proteins. In the absence of fibronectin fibrils, adhesion plaque-like structures can be formed, but these are aberrant in size, location and fine structure.

Prunella vulgarisAttenuates Diabetic Renal Injury by Suppressing Glomerular Fibrosis and Inflammation

2017 ◽  
Vol 45 (03) ◽  
pp. 475-495 ◽  
Author(s):  
Seung Namgung ◽  
Jung Joo Yoon ◽  
Chi-Su Yoon ◽  
Byung Hyuk Han ◽  
Eun Sik Choi ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Staining Intensity ◽  
Collagen Iv ◽  
Diabetic Rats ◽  
Tissue Growth ◽  
Inflammatory Factors ◽  
Diabetic Rat ◽  
Dependent Manner ◽  
Prunella Vulgaris ◽  
Monocyte Chemoattractant Protein 1

Diabetic nephropathy is both the most common complication and the leading cause of mortality associated with diabetes. Prunella vulgaris, a well-known traditional medicinal plant, is used for the cure of abscess, scrofula, hypertension and urinary diseases. This study confirmed whether an aqueous extract of Prunella vulgaris (APV) suppresses renal inflammation and fibrosis. In human mesangial cell (HMC), pretreatment of APV attenuated 25[Formula: see text]mM HG-induced suppressed TGF-[Formula: see text] and Smad-2/4 expression; it increased the expression level of Smad-7. Connective tissue growth factor (CTGF) and collagen IV, fibrosis biomarkers, were significantly decreased by APV. APV suppressed inflammatory factors such as intracellular cell adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). APV inhibited activation and translocation of nuclear factor kappa-B (NF-[Formula: see text]B) in HG-stimulated HMCs. Moreover, APV significantly improved HG-induced ROS in a dose-dependent manner. In diabetic rat models, APV significantly decreased blood glucose, blood urea nitrogen (BUN) and ameliorated plasma creatinine (PCr). APV reduced the PAS positivity staining intensity and basement membrane thickening in glomeruli of diabetic rats. Fibrosis related proteins such as collagen IV and TGF-[Formula: see text]1 were also inhibited by APV. These results suggest that APV has a significant protective effect against diabetic renal dysfunction including inflammation and fibrosis through disruption of the TGF-[Formula: see text]/Smad signaling. Therefore, APV may be useful in potential therapies that target glomerulonephritis and glomerulosclerosis, which lead to diabetic nephropathy.

scholarly journals STAT1 regulates interferon-γ-induced angiotensinogen and MCP-1 expression in a bidirectional manner in primary cultured mesangial cells

2020 ◽  
Vol 21 (3) ◽  
pp. 147032032094652
Author(s):  
Harrison M Penrose ◽  
Akemi Katsurada ◽  
Kayoko Miyata ◽  
Maki Urushihara ◽  
Ryousuke Satou
Keyword(s):  
Mesangial Cells ◽  
Interferon Γ ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Dependent Manner ◽  
Monocyte Chemoattractant Protein 1 ◽  
Signal Transducers ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Suppressors Of Cytokine Signaling

Objective: Intrarenal interferon-γ significantly contributes to the development of glomerular injury in which angiotensinogen and monocyte chemoattractant protein 1 levels are elevated. However, the exact nature of the role that interferon-γ plays in regulating angiotensinogen and monocyte chemoattractant protein 1 expression has not been fully delineated. Therefore, the aim of this study was to investigate the role that interferon-γ plays in angiotensinogen and monocyte chemoattractant protein 1 expression. Methods: Primary cultured rat mesangial cells were treated with 0–20 ng/mL interferon-γ for 2, 8 or 24 hours. Expression levels of angiotensinogen, monocyte chemoattractant protein 1, suppressors of cytokine signaling 1, an intracellular suppressor of Janus kinase-signal transducers and activators of transcription signaling and activity of the Janus kinase-signal transducers and activators of transcription pathway were evaluated by reverse transcriptase polymerase chain reaction and western blot analysis. Results: Interferon-γ increased angiotensinogen expression in mesangial cells with maximal augmentation observed following 5 ng/mL interferon-γ at 8 hours of treatment (1.87 ± 0.05, mRNA, relative ratio). Further increases were reduced or absent using higher concentrations of interferon-γ. Following treatments, monocyte chemoattractant protein 1 expression was induced in a linear dose-dependent manner (6.85 ± 0.62-fold by 20 ng/mL interferon-γ at 24 hours). In addition, interferon-γ induced STAT1 phosphorylation and suppressors of cytokine signaling 1 expression in a linear dose-dependent manner. The suppression of STAT1 and suppressors of cytokine signaling 1 expression by small interference RNAs facilitated an increase in interferon-γ-induced angiotensinogen expression, indicating that these two factors negatively regulate angiotensinogen expression. In contrast, the increase in interferon-γ-induced monocyte chemoattractant protein 1 expression was attenuated in STAT1-deficient mesangial cells, suggesting that STAT1 positively regulates monocyte chemoattractant protein 1 expression in mesangial cells. Conclusion: These results demonstrate that while interferon-γ increases both angiotensinogen and monocyte chemoattractant protein 1 expression, STAT1 plays an opposing role in the regulation of each factor in mesangial cells.

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