scholarly journals Mobilization of TLR4 Into Lipid Rafts by Aggregatibacter Actinomycetemcomitans in Gingival Epithelial Cells

2016 ◽  
Vol 39 (5) ◽  
pp. 1777-1786 ◽  
Author(s):  
Haruka Imai ◽  
Tsuyoshi Fujita ◽  
Mikihito Kajiya ◽  
Kazuhisa Ouhara ◽  
Tetsuya Yoshimoto ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Map Kinase ◽  
Lipid Rafts ◽  
Inflammatory Cytokines ◽  
Aggregatibacter Actinomycetemcomitans ◽  
P38 Map Kinase ◽  
Mrna Levels ◽  
Periodontal Pathogens ◽  
Gingival Epithelial Cells ◽  
Tnf Α

Background: An investigation of the mechanisms underlying the production of inflammatory cytokines through the stimulation of microorganisms on gingival epithelial cells may provide insights into the pathogenesis of the initiation of periodontitis. Lipid rafts, microdomains in the cell membrane, include a large number of receptors, and are centrally involved in signal transduction. We herein examined the involvement of lipid rafts in the expression of interleukin (IL-6) and IL-8 in gingival epithelial cells stimulated by periodontal pathogens. Methods: OBA9, a human gingival cell line, was stimulated by Aggregatibacter actinomycetemcomitans or tumor necrosis factor (TNF)-α in the presence of methyl-β-cyclodextrin (MβCD). Results: A. actinomycetemcomitans or TNF-α increased IL-8 and IL-6 mRNA levels, and promoted the phosphorylation of ERK and p38 MAP kinase in OBA9. The pretreatment with MβCD abolished increases in IL-6 and IL-8 mRNA levels and the phosphorylation induced by A. actinomycetemcomitans, but did not suppress the response induced by TNF-α. The transfection of TLR4 inhibited A. actinomycetemcomitans-induced increases in IL-8 and IL-6 mRNA levels. Confocal microscopy revealed that MβCD inhibited the mobilization of TLR4 into lipid rafts. Conclusion: The mobilization of TLR4 into lipid rafts is involved in the expression of inflammatory cytokines and phosphorylation of MAP kinase in human gingival epithelial cells stimulated by A. actinomycetemcomitans.

scholarly journals Interleukin-8 and Intercellular Adhesion Molecule 1 Regulation in Oral Epithelial Cells by Selected Periodontal Bacteria: Multiple Effects of Porphyromonas gingivalis via Antagonistic Mechanisms

2001 ◽  
Vol 69 (3) ◽  
pp. 1364-1372 ◽  
Author(s):  
George T.-J. Huang ◽  
Daniel Kim ◽  
Jonathan K.-H. Lee ◽  
Howard K. Kuramitsu ◽  
Susan Kinder Haake
Keyword(s):  
Epithelial Cells ◽  
Porphyromonas Gingivalis ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Interleukin 8 ◽  
Intercellular Adhesion Molecule ◽  
Mrna Levels ◽  
Periodontal Pathogens ◽  
Intercellular Adhesion Molecule 1 ◽  
Gingival Epithelial Cells

ABSTRACT Interaction of bacteria with mucosal surfaces can modulate the production of proinflammatory cytokines and adhesion molecules produced by epithelial cells. Previously, we showed that expression of interleukin-8 (IL-8) and intercellular adhesion molecule 1 (ICAM-1) by gingival epithelial cells increases following interaction with several putative periodontal pathogens. In contrast, expression of IL-8 and ICAM-1 is reduced after Porphyromonas gingivalis ATCC 33277 challenge. In the present study, we investigated the mechanisms that govern the regulation of these two molecules in bacterially infected gingival epithelial cells. Experimental approaches included bacterial stimulation of gingival epithelial cells by either a brief challenge (1.5 to 2 h) or a continuous coculture throughout the incubation period. The kinetics of IL-8 and ICAM-1 expression following brief challenge were such that (i) secretion of IL-8 by gingival epithelial cells reached its peak 2 h following Fusobacterium nucleatum infection whereas it rapidly decreased within 2 h after P. gingivalis infection and remained decreased up to 30 h and (ii) IL-8 and ICAM-1 mRNA levels were up-regulated rapidly 2 to 4 h postinfection and then decreased to basal levels 8 to 20 h after infection with either Actinobacillus actinomycetemcomitans, F. nucleatum, or P. gingivalis. Attenuation of IL-8 secretion was facilitated by adherent P. gingivalis strains. The IL-8 secreted from epithelial cells after F. nucleatum stimulation could be down-regulated by subsequent infection with P. gingivalisor its culture supernatant. Although these results suggested that IL-8 attenuation at the protein level might be associated with P. gingivalis proteases, the Arg- and Lys-gingipain proteases did not appear to be solely responsible for IL-8 attenuation. In addition, while P. gingivalis up-regulated IL-8 mRNA expression, this effect was overridden when the bacteria were continuously cocultured with the epithelial cells. The IL-8 mRNA levels in epithelial cells following sequential challenge with P. gingivalis andF. nucleatum and vice versa were approximately identical and were lower than those following F. nucleatum challenge alone and higher than control levels or those following P. gingivalis challenge alone. Thus, together with the protease effect, P. gingivalis possesses a powerful strategy to ensure the down-regulation of IL-8 and ICAM-1.

scholarly journals Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study

Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Combination Treatment ◽  
Primary Cultures ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Mrna Levels ◽  
Thyroid Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.

TNF-α and serum induce SKALP/elafin gene expression in human keratinocytes by a p38 MAP kinase-dependent pathway

2000 ◽  
Vol 292 (4) ◽  
pp. 180-187 ◽  
Author(s):  
R. Pfundt ◽  
M. Wingens ◽  
M. Bergers ◽  
M. Zweers ◽  
M. Frenken ◽  
...  
Keyword(s):  
Gene Expression ◽  
Map Kinase ◽  
Human Keratinocytes ◽  
P38 Map Kinase ◽  
Tnf Α ◽  
Dependent Pathway

Inhibition of monocyte-derived inflammatory cytokines by IL-25 occurs via p38 Map kinase–dependent induction of Socs-3

Blood ◽  
2009 ◽  
Vol 113 (15) ◽  
pp. 3512-3519 ◽  
Author(s):  
Roberta Caruso ◽  
Carmine Stolfi ◽  
Massimiliano Sarra ◽  
Angelamaria Rizzo ◽  
Massimo C. Fantini ◽  
...  
Keyword(s):  
Map Kinase ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Human Peripheral Blood ◽  
Serum Levels ◽  
Cell Types ◽  
P38 Map Kinase ◽  
Negative Regulator ◽  
Therapeutic Implications

Abstract IL-25, a member of the IL-17 cytokine family, is known to enhance Th2-like responses associated with increased serum levels of IgE, IgG1, IgA, blood eosinophilia, and eosinophilic infiltrates in various tissues. However, IL-25 also abrogates inflammatory responses driven by Th17 cells. However, the cell types that respond to IL-25 and the mechanisms by which IL-25 differentially regulates immune reactions are not well explored. To identify potential targets of IL-25, we initially examined IL-25 receptor (IL-25R) in human peripheral blood cells. IL-25R was predominantly expressed by CD14+ cells. We next assessed the functional role of IL-25 in modulating the response of CD14+ cells to various inflammatory signals. CD14+ cells responded to IL-25 by down-regulating the synthesis of inflammatory cytokines induced by toll-like receptor (TLR) ligands and inflammatory cytokines. Inhibition of cytokine response by IL-25 occurred via a p38 Map kinase–driven Socs-3–dependent mechanism. In vivo, IL-25 inhibited monocyte-derived cytokines and protected against LPS-induced lethal endotoxemia in mice. These data indicate that IL-25 is a negative regulator of monocyte proinflammatory cytokine responses, which may have therapeutic implications.

scholarly journals PPARγ inhibits airway epithelial cell inflammatory response through a MUC1-dependent mechanism

2012 ◽  
Vol 302 (7) ◽  
pp. L679-L687 ◽  
Author(s):  
Yong Sung Park ◽  
Erik P. Lillehoj ◽  
Kosuke Kato ◽  
Choon Sik Park ◽  
Kwang Chul Kim
Keyword(s):  
Epithelial Cells ◽  
Culture Media ◽  
A549 Cells ◽  
Luciferase Reporter ◽  
Muc1 Expression ◽  
Mrna Levels ◽  
Airway Epithelial ◽  
Pparγ Agonist ◽  
Tnf Α ◽  
Primary Mouse

This study was conducted to examine the relationship between the peroxisome proliferator-associated receptor-γ (PPARγ) and MUC1 mucin, two anti-inflammatory molecules expressed in the airways. Treatment of A549 lung epithelial cells or primary mouse tracheal surface epithelial (MTSE) cells with phorbol 12-myristate 13-acetate (PMA) increased the levels of tumor necrosis factor (TNF)-α in cell culture media compared with cells treated with vehicle alone. Overexpression of MUC1 in A549 cells decreased PMA-stimulated TNF-α levels, whereas deficiency of Muc1 expression in MTSE cells from Muc1 null mice increased PMA-induced TNF-α levels. Treatment of A549 or MTSE cells with the PPARγ agonist troglitazone (TGN) blocked the ability of PMA to stimulate TNF-α levels. However, the effect of TGN required the presence of MUC1/Muc1, since no differences in TNF-α levels were seen between PMA and PMA plus TGN in MUC1/Muc1-deficient cells. Similarly, whereas TGN decreased interleukin-8 (IL-8) levels in culture media of MUC1-expressing A549 cells treated with Pseudomonas aeruginosa strain K (PAK), no differences in IL-8 levels were seen between PAK and PAK plus TGN in MUC1-nonexpressing cells. EMSA confirmed the presence of a PPARγ-binding element in the MUC1 gene promoter. Finally, TGN treatment of A549 cells increased MUC1 promoter activity measured using a MUC1-luciferase reporter gene, augmented MUC1 mRNA levels by quantitative RT-PCR, and enhanced MUC1 protein expression by Western blot analysis. These combined data are consistent with the hypothesis that PPARγ stimulates MUC1/Muc1 expression, thereby blocking PMA/PAK-induced TNF-α/IL-8 production by airway epithelial cells.

scholarly journals TNF-α Expression in Oral Candida albicans-Infected Human Gingival Epithelial Cells

2011 ◽  
Vol 10 (2) ◽  
pp. 77-82 ◽  
Author(s):  
Yoko Tanaka ◽  
Lin Zhang ◽  
Tonami Ikuta ◽  
Joutaro Omori ◽  
Hirotaka Omine ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Gingival Epithelial Cells ◽  
Tnf Α ◽  
Oral Candida ◽  
Human Gingival Epithelial Cells

scholarly journals Cytokine-Mediated Downregulation of Coxsackievirus-Adenovirus Receptor in Endothelial Cells

2004 ◽  
Vol 78 (15) ◽  
pp. 8047-8058 ◽  
Author(s):  
Theresa Vincent ◽  
Ralf F. Pettersson ◽  
Ronald G. Crystal ◽  
Philip L. Leopold
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cells ◽  
Protein Expression ◽  
Western Blot ◽  
Inflammatory Cytokines ◽  
Cell Physiology ◽  
Mrna Levels ◽  
Cytokine Treatment ◽  
Adenovirus Receptor ◽  
The Impact

ABSTRACT Endothelial cells have the ability to change their complement of cell surface proteins in response to inflammatory cytokines. We hypothesized that the expression of the coxsackievirus-adenovirus receptor (CAR), a viral receptor and putative cell-cell adhesion molecule, may be altered during the response of endothelial cells to inflammation. To test this hypothesis, we evaluated CAR protein and mRNA levels in human umbilical vein endothelial cells after they were exposed to tumor necrosis factor alpha, gamma interferon, or a combination of the two cytokines. Flow cytometric and Western blot analyses indicated that cytokine treatment led to a synergistic decrease in CAR protein expression. A Western blot analysis showed that CAR levels decreased to 16% ± 4% or 1% ± 4% of the CAR protein levels in untreated cells with either 24 or 48 h of cytokine treatment, respectively. Quantitative reverse transcription-PCR demonstrated that the combination treatment caused CAR mRNA levels to decrease to 21% ± 12% or 5% ± 3% of the levels in untreated cells after a 24- or 48-h cytokine treatment, respectively. Reduced CAR expression led to a decrease in adenovirus (Ad) binding of 80% ± 3% (compared with untreated endothelial cells), with a subsequent decrease in Ad-mediated gene transfer that was dependent on the dose and duration of cytokine treatment but not on the dose of Ad. A similar decrease in CAR protein level and susceptibility to Ad infection was observed in human microvascular endothelial cells, while CAR expression on normal human bronchial epithelial cells or A549 lung epithelial cells was less affected by cytokine treatments. Taken together, the data demonstrate that inflammatory cytokines decrease CAR mRNA and protein expression with a concomitant decrease in Ad binding, reflecting the impact of cell physiology on the function of CAR and the potential effect of inflammation on the ability of Ad to transfer genes to endothelial cells.

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