MMPs contribute to TNF-α-induced alteration of the blood-cerebrospinal fluid barrier in vitro

2007 ◽  
Vol 293 (3) ◽  
pp. C855-C864 ◽  
Author(s):  
Patrick Zeni ◽  
Eva Doepker ◽  
Ulf Schulze Topphoff ◽  
Sabine Huewel ◽  
Tobias Tenenbaum ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Epithelial Cells ◽  
Choroid Plexus ◽  
Adhesion Molecule ◽  
Cellular Adhesion ◽  
Matrix Metalloproteases ◽  
Intercellular Adhesion Molecule ◽  
Tnf Α ◽  
The Impact

The epithelial cells of the choroid plexus separate the central nervous system from the blood forming the blood-cerebrospinal fluid (CSF) barrier. The choroid plexus is the main source of CSF, whose composition is markedly changed during pathological disorders, for example regarding matrix metalloproteases (MMPs) and tissue inhibitors of matrix metalloproteases (TIMPs). In the present study, we analyzed the impact of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) on the blood-CSF barrier using an in vitro model based on porcine choroid plexus epithelial cells (PCPEC). TNF-α evoked distinct inflammatory processes as shown by mRNA upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. The cytokine caused a drastic decrease in transepithelial electrical resistance within several hours representing an enhanced permeability of PCPEC monolayers. In addition, the distribution of tight junction proteins was altered. Moreover, MMP activity in PCPEC supernatants was significantly increased by TNF-α, presumably due to a diminished expression of TIMP-3 that was similarly observed. MMP-2, -3, and -9 as well as TIMP-1 and -2 were also analyzed and found to be differentially regulated by the cytokine. The TNF-α-induced breakdown of the blood-CSF barrier could partially be blocked by the MMP inhibitor GM-6001. Our results show a contribution of MMPs to the inflammatory breakdown of the blood-CSF barrier in vitro. Thus TNF-α may mediate the binding of leukocytes to cellular adhesion molecules and the transmigration across the blood-CSF barrier.

IL-4 induces ICAM-1 expression in human bronchial epithelial cells and potentiates TNF-α

1999 ◽  
Vol 277 (1) ◽  
pp. L58-L64 ◽  
Author(s):  
Ilja Striz ◽  
Tadashi Mio ◽  
Yuichi Adachi ◽  
Peggy Heires ◽  
Richard A. Robbins ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Adhesion Molecule ◽  
Airway Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Intercellular Adhesion Molecule ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Macrophage Cells ◽  
Tnf Α

Interleukin (IL)-4 is thought to contribute to the Th2 type of immune response and hence the development of allergic reactions such as asthma. In asthmatic patients, the airway epithelium expresses increased amounts of the cell surface adhesion molecule intercellular adhesion molecule (ICAM)-1 (CD54). One cytokine capable of inducing ICAM-1 in airway epithelial cells, tumor necrosis factor-α (TNF-α), is present in asthma. This study evaluated if IL-4 either alone or together with TNF-α costimulation might modulate CD54 expression by human bronchial epithelial cells (HBECs). CD54 positivity increased in response to IL-4 (16 ± 2% positive vs. 3 ± 1%, P < 0.01); greater induction of CD54 resulted from TNF-α (45 ± 2%, P < 0.001). Costimulation with TNF-α plus IL-4 further augmented expression (56 ± 1%, P < 0.05). Immunoperoxidase results were confirmed by flow cytometry. RT-PCR revealed no increase in ICAM-1 mRNA expression under control conditions or after stimulation with IL-4 alone. TNF-α increased IL-4 mRNA, and IL-4 potentiated this. Functionally, IL-4 augmented the adhesion of THP-1 monocyte/macrophage cells to monolayers of HBECs both alone and in the presence of TNF-α. We conclude that 1) IL-4 augments epithelial cell ICAM-1 expression, 2) IL-4 potentiates the adhesion of THP-1 monocyte/macrophage cells to epithelial cells, and 3) modulation of epithelial cell ICAM-1 expression by IL-4 may play a role in the immunopathology of bronchial asthma.

scholarly journals Invasion of Human Mucosal Epithelial Cells by Neisseria gonorrhoeae Upregulates Expression of Intercellular Adhesion Molecule 1 (ICAM-1)

1999 ◽  
Vol 67 (3) ◽  
pp. 1149-1156 ◽  
Author(s):  
Gary A. Jarvis ◽  
Jing Li ◽  
Karen V. Swanson
Keyword(s):  
Flow Cytometry ◽  
B Cells ◽  
Epithelial Cells ◽  
Neisseria Gonorrhoeae ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Invasive Strain

ABSTRACT Infection of the mucosa by Neisseria gonorrhoeaeinvolves adherence to and invasion of epithelial cells. Little is known, however, about the expression by mucosal epithelial cells of molecules that mediate cellular interactions between epithelial cells and neutrophils at the site of gonococcal infection. The aim of this study was to determine the expression of intercellular adhesion molecule 1 (ICAM-1) by epithelial cells during the process of gonococcal invasion. The highly invasive strain FA1090 and the poorly invasive strain MS11 were incubated with human endometrial adenocarcinoma (HEC-1-B) or human cervical carcinoma (ME-180) epithelial cells, after which ICAM-1 expression was measured by flow cytometry. After 15 h of infection with FA1090, expression of ICAM-1 increased 4.7- and 2.1-fold for HEC-1-B and ME-180 cells, respectively, whereas 15 h of infection of HEC-1-B cells with MS11 increased ICAM-1 expression only 1.6-fold. ICAM-1 expression was restricted to the cell surface, since no soluble ICAM-1 was detected. The distribution of staining was heterogeneous and mimicked that seen after treatment of HEC-1-B cells with the ICAM-1 agonist tumor necrosis factor alpha (TNF-α) in the absence of bacteria. PCR and dot blot analyses of ICAM-1 mRNA showed no change in levels over time in response to infection. Although TNF-α was produced by HEC-1-B cells after infection, the extent of ICAM-1 upregulation was not affected by neutralizing anti-TNF-α antiserum. Dual-fluorescence flow cytometry showed that the cells with the highest levels of ICAM-1 expression were cells with associated gonococci. We conclude that epithelial cells upregulate the expression of ICAM-1 in response to infection with invasive gonococci. On the mucosa, upregulation of ICAM-1 by infected epithelial cells may function to maintain neutrophils at the site of infection, thereby reducing further invasion of the mucosa by gonococci.

The impact of selectins on mortality in stable carotid atherosclerosis

2015 ◽  
Vol 114 (09) ◽  
pp. 632-638 ◽  
Author(s):  
Matthias Hoke ◽  
Max-Paul Winter ◽  
Oswald Wagner ◽  
Markus Exner ◽  
Martin Schillinger ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Cardiovascular Mortality ◽  
Carotid Atherosclerosis ◽  
Leukocyte Adhesion ◽  
Inflammatory Cells ◽  
Endothelial Activation ◽  
Cellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
The Impact

SummaryCellular adhesion molecules also known as selectins promote recruitment of inflammatory cells into the arterial wall where they interact with lipid particles leading subsequently to plaque formation. The intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1) and the endothelial-leukocyte adhesion molecule 1 (ELAM-1) also known as E-selectin mediate the attachment of leukocytes and have been implicated in the destabilisation of atherosclerotic plaques. Therefore, we hypothesised that plasma selectin levels are associated with adverse clinical outcome. We prospectively studied 855 patients with sonographically confirmed carotid atherosclerosis. During a median follow-up of 6.2 years, corresponding to 5,551 overall person-years, 275 patients (26 %) died. We detected a significant association between cardiovascular mortality and ICAM-1 (adjusted hazard ratio [HR]: 3.43, 95 % confidence interval [CI] 2.00–5.88, p< 0.001) as well as VCAM-1 (adjusted HR: 2.51, 95 % CI 1.45–4.34, p=0.001) when comparing the fourth with the first quartile. Comparable results were obtained for all-cause mortality. In contrast, we could not detect a significant association between E-selectin and all-cause or cardiovascular mortality. We identified the selectins ICAM-1 and VCAM-1 as strong and independent predictors of all-cause and cardiovascular mortality in patients with stable carotid atherosclerosis. These molecules are elevated in states of endothelial activation and might assist to monitor anti-atherosclerotic therapy and select those patients with carotid atherosclerosis, who are at higher risk for cardiovascular events.

scholarly journals Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study

2021 ◽  
Vol 18 (2) ◽  
pp. 483
Author(s):  
Na An ◽  
Jasmin Holl ◽  
Xuekui Wang ◽  
Marco Aoqi Rausch ◽  
Oleh Andrukhov ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Periodontal Diseases ◽  
Suppressive Effect ◽  
Cell Surface Expression ◽  
Epithelial Cell Line ◽  
Oral Epithelial Cells ◽  
Tnf Α ◽  
Oral Epithelial ◽  
The Impact

Smoking is a well-recognized risk factor for oral mucosal and periodontal diseases. Nicotine is an important component of cigarette smoke. This study aims to investigate the impact of nicotine on the viability and inflammatory mediator production of an oral epithelial cell line in the presence of various inflammatory stimuli. Oral epithelial HSC-2 cells were challenged with nicotine (10−8–10−2 M) for 24 h in the presence or absence of Porphyromonas gingivalis lipopolysaccharide (LPS, 1 µg/mL) or tumor necrosis factor (TNF)-α (10−7 M) for 24 h. The cell proliferation/viability was determined by MTT assay. Gene expression of interleukin (IL)-8, intercellular adhesion molecule (ICAM)-1, and β-defensin was assayed by qPCR. The production of IL-8 protein and cell surface expression of ICAM-1 was assessed by ELISA and flow cytometry, respectively. Proliferation/viability of HSC-2 cells was unaffected by nicotine at concentrations up to 10−3 M and inhibited at 10−2 M. Nicotine had no significant effect on the basal expression of IL-8, ICAM-1, and β-defensin. At the same time, it significantly diminished P. gingivalis LPS or the TNF-α-induced expression levels of these factors. Within the limitations of this study, the first evidence was provided in vitro that nicotine probably exerts a suppressive effect on the production of inflammatory mediators and antimicrobial peptides in human oral epithelial cells.

scholarly journals Immune response and pathogen invasion at the choroid plexus in the onset of cerebral toxoplasmosis

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Caio Andreeta Figueiredo ◽  
Johannes Steffen ◽  
Lorena Morton ◽  
Sushmitha Arumugam ◽  
Oliver Liesenfeld ◽  
...  
Keyword(s):  
Immune Response ◽  
Endothelial Cells ◽  
Epithelial Cells ◽  
Choroid Plexus ◽  
The Body ◽  
Potential Contribution ◽  
Pathogen Invasion ◽  
The Impact

Abstract Background Toxoplasma gondii (T. gondii) is a highly successful parasite being able to cross all biological barriers of the body, finally reaching the central nervous system (CNS). Previous studies have highlighted the critical involvement of the blood–brain barrier (BBB) during T. gondii invasion and development of subsequent neuroinflammation. Still, the potential contribution of the choroid plexus (CP), the main structure forming the blood–cerebrospinal fluid (CSF) barrier (BCSFB) have not been addressed. Methods To investigate T. gondii invasion at the onset of neuroinflammation, the CP and brain microvessels (BMV) were isolated and analyzed for parasite burden. Additionally, immuno-stained brain sections and three-dimensional whole mount preparations were evaluated for parasite localization and morphological alterations. Activation of choroidal and brain endothelial cells were characterized by flow cytometry. To evaluate the impact of early immune responses on CP and BMV, expression levels of inflammatory mediators, tight junctions (TJ) and matrix metalloproteinases (MMPs) were quantified. Additionally, FITC-dextran was applied to determine infection-related changes in BCSFB permeability. Finally, the response of primary CP epithelial cells to T. gondii parasites was tested in vitro. Results Here we revealed that endothelial cells in the CP are initially infected by T. gondii, and become activated prior to BBB endothelial cells indicated by MHCII upregulation. Additionally, CP elicited early local immune response with upregulation of IFN-γ, TNF, IL-6, host-defence factors as well as swift expression of CXCL9 chemokine, when compared to the BMV. Consequently, we uncovered distinct TJ disturbances of claudins, associated with upregulation of MMP-8 and MMP-13 expression in infected CP in vivo, which was confirmed by in vitro infection of primary CP epithelial cells. Notably, we detected early barrier damage and functional loss by increased BCSFB permeability to FITC-dextran in vivo, which was extended over the infection course. Conclusions Altogether, our data reveal a close interaction between T. gondii infection at the CP and the impairment of the BCSFB function indicating that infection-related neuroinflammation is initiated in the CP.

scholarly journals Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor α in endothelium

1998 ◽  
Vol 331 (3) ◽  
pp. 853-861 ◽  
Author(s):  
Toshiyuki ARAI ◽  
Susan A. KELLY ◽  
Matthew L. BRENGMAN ◽  
Manabu TAKANO ◽  
Elise H. SMITH ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Adhesion Molecule ◽  
Tumour Necrosis ◽  
Intercellular Adhesion Molecule ◽  
Tumour Necrosis Factor Α ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Proinflammatory cytokines upregulate endothelial adhesion molecule expression, thereby initiating the microvascular inflammatory response. We re-evaluated the reported role of reactive oxygen metabolites (ROMs) in signalling upregulation of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by tumour necrosis factor α (TNF-α) in vitro. TNF-α upregulation of endothelial-cell ICAM-1 expression was inhibited by the cell-permeable antioxidants, or by the adenovirus-mediated intracellular overexpression of Cu,Zn-superoxide dismutase, but not by the exogenous (extracellular) administration of the cell-impermeable antioxidants, superoxide dismutase and/or catalase. This ICAM-1 upregulation was also inhibited by inhibitors of NADH dehydrogenase, cytochrome bc1 complex and NADPH oxidase. However, a measurable increase in net cellular ROM generation in response to TNF-α was not seen using four disparate sensitive ROM assays. Moreover, the stimulation of exogenous or endogenous ROM generation did not upregulate ICAM-1, nor enhance ICAM-1 upregulation by TNF-α. These findings suggest that an ambient background flux of ROMs, generated intracellularly, but not their net incremental generation, is necessary for TNF-α to induce ICAM-1 expression in endothelium in vitro.

scholarly journals Echovirus-30 Infection Alters Host Proteins in Lipid Rafts at the Cerebrospinal Fluid Barrier In Vitro

2020 ◽  
Vol 8 (12) ◽  
pp. 1958
Author(s):  
Marie Wiatr ◽  
Simon Staubach ◽  
Ricardo Figueiredo ◽  
Carolin Stump-Guthier ◽  
Hiroshi Ishikawa ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Lipid Rafts ◽  
Choroid Plexus Papilloma ◽  
Cellular Adhesion ◽  
Host Cells ◽  
Mass Spectrometry Analysis ◽  
Enteroviral Infection ◽  
Echovirus 30 ◽  
The Impact

Echovirus-30 (E-30) is a non-polio enterovirus responsible for meningitis outbreaks in children worldwide. To gain access to the central nervous system (CNS), E-30 first has to cross the blood-brain barrier (BBB) or the blood-cerebrospinal fluid barrier (BCSFB). E-30 may use lipid rafts of the host cells to interact with and to invade the BCSFB. To study enteroviral infection of the BCSFB, an established in vitro model based on human immortalized brain choroid plexus papilloma (HIBCPP) cells has been used. Here, we investigated the impact of E-30 infection on the protein content of the lipid rafts at the BCSFB in vitro. Mass spectrometry analysis following E-30 infection versus uninfected conditions revealed differential abundancy in proteins implicated in cellular adhesion, cytoskeleton remodeling, and endocytosis/vesicle budding. Further, we evaluated the blocking of endocytosis via clathrin/dynamin blocking and its consequences for E-30 induced barrier disruption. Interestingly, blocking of endocytosis had no impact on the capacity of E-30 to induce loss of barrier properties in HIBCPP cells. Altogether, these data highlight the impact of E-30 on HIBCPP cells microdomain as an important factor for host cell alteration.

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