scholarly journals The Fusion Protein rFlaA:Betv1 Modulates DC Responses by a p38-MAPK and COX2-Dependent Secretion of PGE2 from Epithelial Cells

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3415
Author(s):  
Yen-Ju Lin ◽  
Adam Flaczyk ◽  
Sonja Wolfheimer ◽  
Alexandra Goretzki ◽  
Annette Jamin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Fusion Protein ◽  
P38 Mapk ◽  
Intracellular Signaling ◽  
Birch Pollen ◽  
Pollen Allergy ◽  
Airway Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Myeloid Dendritic Cells

Developing new adjuvants/vaccines and better understanding their mode-of-action is an important task. To specifically improve birch pollen allergy treatment, we designed a fusion protein consisting of major birch pollen allergen Betv1 conjugated to the TLR5-ligand flagellin (rFlaA:Betv1). This study investigates the immune-modulatory effects of rFlaA:Betv1 on airway epithelial cells. LA-4 mouse lung epithelial cells were stimulated with rFlaA:Betv1 in the presence/absence of various inhibitors with cytokine- and chemokine secretion quantified by ELISA and activation of intracellular signaling cascades demonstrated by Western blot (WB). Either LA-4 cells or LA-4-derived supernatants were co-cultured with BALB/c bone marrow-derived myeloid dendritic cells (mDCs). Compared to equimolar amounts of flagellin and Betv1 provided as a mixture, rFlaA:Betv1 induced higher secretion of IL-6 and the chemokines CCL2 and CCL20 from LA-4 cells and a pronounced MAPK- and NFκB-activation. Mechanistically, rFlaA:Betv1 was taken up more strongly and the induced cytokine production was inhibited by NFκB-inhibitors, while ERK- and p38-MAPK-inhibitors only suppressed IL-6 and CCL2 secretion. In co-cultures of LA-4 cells with mDCs, rFlaA:Betv1-stimulated LA-4 cells p38-MAPK- and COX2-dependently secreted PGE2, which modulated DC responses by suppressing pro-inflammatory IL-12 and TNF-α secretion. Taken together, these results contribute to our understanding of the mechanisms underlying the strong immune-modulatory effects of flagellin-containing fusion proteins.

scholarly journals Intelectin is required for IL-13-induced monocyte chemotactic protein-1 and -3 expression in lung epithelial cells and promotes allergic airway inflammation

2010 ◽  
Vol 298 (3) ◽  
pp. L290-L296 ◽  
Author(s):  
Naibing Gu ◽  
Guannan Kang ◽  
Chang'E Jin ◽  
Yongjian Xu ◽  
Zhenxiang Zhang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Airway Epithelium ◽  
Allergic Airway Inflammation ◽  
Airway Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Airway Epithelial ◽  
Chemotactic Protein ◽  
Lung Epithelial

Asthma is characterized by airway inflammation, mucus overproduction, airway hyperreactivity, and peribronchial fibrosis. Intelectin has been shown to be increased in airway epithelium of asthmatics. However, the role of intelectin in the pathogenesis of asthma is unknown. Airway epithelial cells can secrete chemokines such as monocyte chemotactic protein (MCP)-1 and -3 that play crucial roles in asthmatic airway inflammation. We hypothesized that intelectin plays a role in allergic airway inflammation by regulating chemokine expression. In a mouse allergic asthma model, we found that mRNA expression of intelectin-2 as well as MCP-1 and -3 in mouse lung was increased very early (within 2 h) after allergen challenge. Expression of intelectin protein was localized to mucous cells in airway epithelium. Treatment of MLE12 mouse lung epithelial cells with interleukin IL-13, a critical mediator of allergic airway disease, induced expression of intelectin-1 and -2 as well as MCP-1 and -3. When IL-13-induced intelectin-1 and -2 expression was inhibited by RNA interference, IL-13-induced extracellular signal-regulated kinase 1/2 phosphorylation and MCP-1 and -3 production by MLE12 cells was inhibited. Furthermore, inhibition of intelectin expression by airway transfection with shRNA targeting intelectin-1 and -2 attenuated allergen-induced airway inflammation. We conclude that intelectin, a molecule expressed by airway epithelial cells and upregulated in asthma, is required for IL-13-induced MCP-1 and -3 production in mouse lung epithelial cells and contributes to allergic airway inflammation.

scholarly journals Asymmetric dimethylarginine potentiates lung inflammation in a mouse model of allergic asthma

2010 ◽  
Vol 299 (6) ◽  
pp. L816-L825 ◽  
Author(s):  
Elizabeth Klein ◽  
Jason Weigel ◽  
Mary C. Buford ◽  
Andrij Holian ◽  
Sandra M. Wells
Keyword(s):  
Epithelial Cells ◽  
Lung Inflammation ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Airway Epithelial Cells ◽  
Inos Expression ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Lung Epithelial

Nitric oxide (NO), formed by nitric oxide synthase (NOS), is an important mediator of lung inflammation in allergic asthma. Asymmetric dimethylarginine (ADMA), a competitive endogenous inhibitor of NOS, is metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Elevated ADMA has been shown to affect lung function in mice, and by inhibiting NOS it alters NO and reactive oxygen species production in mouse lung epithelial cells. However, the effects of altered ADMA levels during lung inflammation have not been explored. A model of allergen-induced airway inflammation was utilized in combination with the modulation of endogenous circulating ADMA levels in mice. Airway inflammation was assessed by quantifying inflammatory cell infiltrates in lung lavage and by histology. Lung DDAH expression was assessed by quantitative PCR and immunohistochemistry. Nitrite levels were determined in lung lavage fluid as a measure of NO production. iNOS expression was determined by immunohistochemistry, immunofluorescence, Western blot, and quantitative PCR. NF-κB binding activity was assessed by a transcription factor binding assay. Allergen-induced lung inflammation was potentiated in mice with elevated circulating ADMA and was reduced in mice overexpressing DDAH. Elevated ADMA reduced nitrite levels in lung lavage fluid in both allergen-challenged and control animals. ADMA increased iNOS expression in airway epithelial cells in vivo following allergen challenge and in vitro in stimulated mouse lung epithelial cells. ADMA also increased NF-κB binding activity in airway epithelial cells in vitro. These data support that ADMA may play a role in inflammatory airway diseases such as asthma through modulation of iNOS expression in lung epithelial cells.

scholarly journals Effect of Slit/Robo signaling on regeneration in lung emphysema

2021 ◽  
Author(s):  
Jin-Soo Park ◽  
RyeonJin Cho ◽  
Eun-Young Kang ◽  
Yeon-Mok Oh
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Chronic Obstructive ◽  
Irreversible Damage ◽  
Lung Epithelial ◽  
And Migration ◽  
Proliferation And Migration

AbstractEmphysema, a pathological component of chronic obstructive pulmonary disease, causes irreversible damage to the lung. Previous studies have shown that Slit plays essential roles in cell proliferation, angiogenesis, and organ development. In this study, we evaluated the effect of Slit2 on the proliferation and migration of mouse lung epithelial cells and its role in regeneration in an emphysema lung mouse model. Here, we have shown that Slit2/Robo signaling contributes to the regeneration of lungs damaged by emphysema. Mouse epithelial lung cells treated with Slit2 exhibited increased proliferation and migration in vitro. Our results also showed that Slit2 administration improved alveolar regeneration in the emphysema mouse model in vivo. Furthermore, Slit2/Robo signaling increased the phosphorylation of ERK and Akt, which was mediated by Ras activity. These Slit2-mediated cellular signaling processes may be involved in the proliferation and migration of mouse lung epithelial cells and are also associated with the potential mechanism of lung regeneration. Our findings suggest that Slit2 administration may be beneficial for alveolar regeneration in lungs damaged by emphysema.

scholarly journals Ex vivo model of non‑small cell lung cancer using mouse lung epithelial cells

2017 ◽  
Author(s):  
Taku Sato ◽  
Mami Morita ◽  
Ryota Tanaka ◽  
Yui Inoue ◽  
Miyuki Nomura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Cells ◽  
Small Cell Lung Cancer ◽  
Ex Vivo ◽  
Small Cell ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Small Cell Lung ◽  
Ex Vivo Model ◽  
Lung Epithelial

scholarly journals Mycobacterium tuberculosis Up-Regulates Matrix Metalloproteinase-1 Secretion from Human Airway Epithelial Cells via a p38 MAPK Switch

2005 ◽  
Vol 175 (8) ◽  
pp. 5333-5340 ◽  
Author(s):  
Paul T. G. Elkington ◽  
Jenny E. Emerson ◽  
Laura D. C. Lopez-Pascua ◽  
Cecilia M. O’Kane ◽  
Donna E. Horncastle ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Epithelial Cells ◽  
Matrix Metalloproteinase ◽  
P38 Mapk ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Matrix Metalloproteinase 1 ◽  
Human Airway Epithelial Cells

scholarly journals Stimulant-Dependent Modulation of Cytokines and Chemokines by Airway Epithelial Cells: Cross Talk between Pulmonary Epithelial and Peripheral Blood Mononuclear Cells

2002 ◽  
Vol 9 (1) ◽  
pp. 126-131 ◽  
Author(s):  
Teresa Krakauer
Keyword(s):  
Epithelial Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Peripheral Blood Mononuclear ◽  
Cytokines And Chemokines ◽  
Blood Mononuclear Cells

ABSTRACT Staphylococcal exotoxins (SE) and lipopolysaccharide (LPS) stimulate cells of the immune system to produce proinflammatory cytokines and chemokines which mediate septic shock and acute lung inflammation. A coculture of human peripheral blood mononuclear cells (PBMC) and pulmonary A549 epithelial cells was used to investigate inflammatory responses triggered by staphylococcal enterotoxin B (SEB), toxic shock syndrome toxin 1, and LPS. The levels of interleukin 1β (IL-1β), IL-6, gamma interferon-inducible protein 10, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1α, and RANTES were enhanced by 3.8-, 4.2-, 3.1-, 8.9-, 2-, and 2.9-fold, respectively, in cocultures of SEB-stimulated cells compared to in SEB-stimulated PBMC. In LPS-stimulated cocultures, only MCP-1 and RANTES levels were increased. These data suggest that the modulation of specific cytokines and chemokines is dependent on the stimulus and that there is bidirectional interaction between PBMC and lung epithelial cells to influence the immune response to these different stimuli.

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