Differential regulation of hyaluronan-induced IL-8 and IP-10 in airway epithelial cells

2006 ◽  
Vol 291 (3) ◽  
pp. L479-L486 ◽  
Author(s):  
Sada Boodoo ◽  
Ernst W. Spannhake ◽  
Jonathan D. Powell ◽  
Maureen R. Horton
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cells ◽  
Airway Inflammation ◽  
Immune Modulation ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Airway Epithelial Cells ◽  
Differential Regulation ◽  
Airway Epithelial ◽  
Chemokine Production

Airway epithelium is emerging as a regulator of local inflammation and immune responses. However, the cellular and molecular mechanisms responsible for the immune modulation by these cells have yet to be fully elucidated. At the cellular level, the hallmarks of airway inflammation are mucus gland hypertrophy with excess mucus production, accumulation of inflammatory mediators, inflammation in the airway walls and lumen, and breakdown and turnover of the extracellular matrix. We demonstrate that fragments of the extracellular matrix component hyaluronan induce inflammatory chemokine production in primary airway epithelial cells grown at an air-liquid interface. Furthermore, hyaluronan fragments use two distinct molecular pathways to induce IL-8 and IFN-γ-inducible protein 10 (IP-10) chemokine expression in airway epithelial cells. Hyaluronan-induced IL-8 requires the MAP kinase pathway, whereas hyaluronan-induced IP-10 utilizes the NF-κB pathway. The induction is specific to low-molecular-weight hyaluronan fragments as other glycosaminoglycans do not induce IL-8 and IP-10 in airway epithelial cells. We hypothesize that not only is the extracellular matrix a target of destruction in airway inflammation but it plays a critical role in perpetuating inflammation through the induction of cytokines, chemokines, and modulatory enzymes in epithelial cells. Furthermore, hyaluronan, by inducing IL-8 and IP-10 by distinct pathways, provides a unique target for differential regulation of key inflammatory chemokines.

17,18-Epoxyeicosatetraenoic Acid Inhibits TNF-α-Induced Inflammation in Cultured Human Airway Epithelium and LPS-Induced Murine Airway Inflammation

2021 ◽  
pp. 194589242110276
Author(s):  
Shiori Hara ◽  
Ichiro Tojima ◽  
Shino Shimizu ◽  
Hideaki Kouzaki ◽  
Takeshi Shimizu
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Neutrophil Infiltration ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Mucus Production ◽  
Chemokine Production ◽  
In Vivo Effects

Background 17,18-Epoxyeicosatetraenoic acid (17,18-EpETE), an eicosapentaenoic acid metabolite, is generated from dietary oil in the gut, and antiinflammatory activity of 17,18-EpETE was recently reported. Objective To evaluate the inhibitory effects of 17,18-EpETE in airway inflammation, we examined in vitro and in vivo effects on mucus production, neutrophil infiltration, and cytokine/chemokine production in airway epithelium. Methods Nasal tissue localization of G protein-coupled receptor 40 (GPR40), a receptor of 17,18-EpETE, was determined by immunohistochemical staining. Expression of GPR40 mRNA in nasal mucosa of chronic rhinosinusitis (CRS) patients and control subjects was determined by reverse transcription-polymerase chain reaction (RT-PCR). The in vitro effects on airway epithelial cells were examined using normal human bronchial epithelial cells and NCI-H292 cells. To examine the in vivo effects of 17,18-EpETE on airway inflammation, we induced goblet cell metaplasia, mucus production, and neutrophil infiltration in mouse nasal epithelium by intranasal lipopolysaccharide (LPS) instillation. Results GPR40 is mainly expressed in human nasal epithelial cells and submucosal gland cells. RT-PCR analysis revealed that the expression of GPR40 mRNA was increased in nasal tissues from CRS patients compared with those from control subjects. 17,18-EpETE significantly inhibited tumor necrosis factor (TNF)-α-induced production of interleukin (IL)-6 , IL-8, and mucin from cultured human airway epithelial cells dose dependently, and these antiinflammatory effects on cytokine production were abolished by GW1100, a selective GPR40 antagonist. Intraperitoneal injection or intranasal instillation of 17,18-EpETE significantly attenuated LPS-induced mucus production and neutrophil infiltration in mouse nasal epithelium. Inflammatory cytokine/chemokine production in lung tissues and bronchoalveolar lavage fluids was also inhibited. Conclusion These results indicate that 17,18-EpETE plays a regulatory role in mucus hypersecretion and neutrophil infiltration in nasal inflammation. Local or systemic administration may provide a new therapeutic approach for the treatment of intractable airway disease such as CRS.

scholarly journals Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation

Cell Research ◽  
2008 ◽  
Vol 18 (6) ◽  
pp. 649-663 ◽  
Author(s):  
Jing Wu ◽  
Rongqi Duan ◽  
Huibi Cao ◽  
Deborah Field ◽  
Catherine M Newnham ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Airway Epithelial Cells ◽  
Airway Epithelial

scholarly journals FOXO3a regulates rhinovirus-induced innate immune responses in airway epithelial cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Joao Gimenes-Junior ◽  
Nicole Owuar ◽  
Hymavathi Reddy Vari ◽  
Wuyan Li ◽  
Nathaniel Xander ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Lung Inflammation ◽  
Inflammatory Cytokine ◽  
Airway Epithelial Cell ◽  
Critical Role ◽  
Airway Epithelial Cells ◽  
Type I ◽  
Airway Epithelial ◽  
Antiviral Responses

AbstractForkhead transcription factor class O (FOXO)3a, which plays a critical role in a wide variety of cellular processes, was also found to regulate cell-type-specific antiviral responses. Airway epithelial cells express FOXO3a and play an important role in clearing rhinovirus (RV) by mounting antiviral type I and type III interferon (IFN) responses. To elucidate the role of FOXO3a in regulating antiviral responses, we generated airway epithelial cell-specific Foxo3a knockout (Scga1b1-Foxo3a−/−) mice and a stable FOXO3a knockout human airway epithelial cell line. Compared to wild-type, Scga1b1-Foxo3a−/− mice show reduced IFN-α, IFN-β, IFN-λ2/3 in response to challenge with RV or double-stranded (ds)RNA mimic, Poly Inosinic-polycytidylic acid (Poly I:C) indicating defective dsRNA receptor signaling. RV-infected Scga1b1-Foxo3a−/− mice also show viral persistence, enhanced lung inflammation and elevated pro-inflammatory cytokine levels. FOXO3a K/O airway epithelial cells show attenuated IFN responses to RV infection and this was associated with conformational change in mitochondrial antiviral signaling protein (MAVS) but not with a reduction in the expression of dsRNA receptors under unstimulated conditions. Pretreatment with MitoTEMPO, a mitochondrial-specific antioxidant corrects MAVS conformation and restores antiviral IFN responses to subsequent RV infection in FOXO3a K/O cells. Inhibition of oxidative stress also reduces pro-inflammatory cytokine responses to RV in FOXO3a K/O cells. Together, our results indicate that FOXO3a plays a critical role in regulating antiviral responses as well as limiting pro-inflammatory cytokine expression. Based on these results, we conclude that FOXO3a contributes to optimal viral clearance and prevents excessive lung inflammation following RV infection.

Sodium Sulfite Enhances Rhinovirus-Induced Chemokine Production in Airway Epithelial Cells

2012 ◽  
Vol 89 (4) ◽  
pp. 718-722 ◽  
Author(s):  
Yoon Hong Chun ◽  
Hyun Sook Kim ◽  
Huisu Lee ◽  
Sulmui Won ◽  
Jong-seo Yoon ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Sodium Sulfite ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Chemokine Production

scholarly journals Differential regulation of the transcriptomic and secretomic landscape of sensor and effector functions of human airway epithelial cells

2018 ◽  
Vol 11 (3) ◽  
pp. 627-642 ◽  
Author(s):  
Roland Lehmann ◽  
Mario M Müller ◽  
Tilman E Klassert ◽  
Dominik Driesch ◽  
Magdalena Stock ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Differential Regulation ◽  
Airway Epithelial ◽  
Effector Functions ◽  
Human Airway ◽  
Human Airway Epithelial Cells

Decreased expression of uteroglobin-related protein 1 in inflamed mouse airways is mediated by IL-9

2004 ◽  
Vol 287 (6) ◽  
pp. L1193-L1198 ◽  
Author(s):  
Yoshihiko Chiba ◽  
Takashi Kusakabe ◽  
Shioko Kimura
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Inverse Correlation ◽  
Immunohistochemical Analysis ◽  
Secretory Protein ◽  
Airway Epithelial Cells ◽  
Mrna Levels ◽  
Airway Epithelial ◽  
Related Protein ◽  
Interleukin 9

Uteroglobin-related protein 1 (UGRP1) is a secretory protein, highly expressed in epithelial cells of airways. Although an involvement of UGRP1 in the pathogenesis of asthma has been suggested, its function in airways remains unclear. In the present study, a relationship between airway inflammation, UGRP1 expression, and interleukin-9 (IL-9), an asthma candidate gene, was evaluated by using a murine model of allergic bronchial asthma. A severe airway inflammation accompanied by airway eosinophilia and elevation of IL-9 in bronchoalveolar lavage (BAL) fluids was observed after ovalbumin (OVA) challenge to OVA-sensitized mice. In this animal model of airway inflammation, lung Ugrp1 mRNA expression was greatly decreased compared with control mice. A significant inverse correlation between lung Ugrp1 mRNA levels and IL-9 levels in BAL fluid was demonstrated by regression analysis ( r = 0.616, P = 0.023). Immunohistochemical analysis revealed a distinct localization of UGRP1 in airway epithelial cells of control mice, whereas UGRP1 staining was patchy and faint in inflamed airways. Intranasal administration of IL-9 to naive mice decreased the level of Ugrp1 expression in lungs. These findings suggest that UGRP1 is downregulated in inflamed airways, such as allergic asthmatics, and IL-9 might be an important mediator for modulating UGRP1 expression.

scholarly journals Looping of upstream cis-regulatory elements is required for CFTR expression in human airway epithelial cells

2020 ◽  
Vol 48 (7) ◽  
pp. 3513-3524 ◽  
Author(s):  
Monali NandyMazumdar ◽  
Shiyi Yin ◽  
Alekh Paranjapye ◽  
Jenny L Kerschner ◽  
Hannah Swahn ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Gene Promoter ◽  
Regulatory Elements ◽  
Airway Epithelial Cells ◽  
Control Mechanisms ◽  
Airway Epithelial ◽  
Cell Type ◽  
Long Range Interactions ◽  
Cell Type Specific

Abstract The CFTR gene lies within an invariant topologically associated domain (TAD) demarcated by CTCF and cohesin, but shows cell-type specific control mechanisms utilizing different cis-regulatory elements (CRE) within the TAD. Within the respiratory epithelium, more than one cell type expresses CFTR and the molecular mechanisms controlling its transcription are likely divergent between them. Here, we determine how two extragenic CREs that are prominent in epithelial cells in the lung, regulate expression of the gene. We showed earlier that these CREs, located at −44 and −35 kb upstream of the promoter, have strong cell-type-selective enhancer function. They are also responsive to inflammatory mediators and to oxidative stress, consistent with a key role in CF lung disease. Here, we use CRISPR/Cas9 technology to remove these CREs from the endogenous locus in human bronchial epithelial cells. Loss of either site extinguished CFTR expression and abolished long-range interactions between these sites and the gene promoter, suggesting non-redundant enhancers. The deletions also greatly reduced promoter interactions with the 5′ TAD boundary. We show substantial recruitment of RNAPII to the −35 kb element and identify CEBPβ as a key activator of airway expression of CFTR, likely through occupancy at this CRE and the gene promoter.

scholarly journals Virus Infection-Induced Bronchial Asthma Exacerbation

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Mutsuo Yamaya
Keyword(s):  
Epithelial Cells ◽  
Viral Infection ◽  
Airway Inflammation ◽  
Bronchial Asthma ◽  
Inflammatory Mediators ◽  
Asthma Exacerbation ◽  
Viral Infections ◽  
Inflammatory Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial

Infection with respiratory viruses, including rhinoviruses, influenza virus, and respiratory syncytial virus, exacerbates asthma, which is associated with processes such as airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. In patients with viral infections and with infection-induced asthma exacerbation, inflammatory mediators and substances, including interleukins (ILs), leukotrienes and histamine, have been identified in the airway secretions, serum, plasma, and urine. Viral infections induce an accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Viral infections also enhance the production of inflammatory mediators and substances in airway epithelial cells, mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect the barrier function of the airway epithelial cells and vascular endothelial cells. Recent reports have demonstrated augmented viral production mediated by an impaired interferon response in the airway epithelial cells of asthma patients. Several drugs used for the treatment of bronchial asthma reduce viral and pro-inflammatory cytokine release from airway epithelial cells infected with viruses. Here, I review the literature on the pathogenesis of the viral infection-induced exacerbation of asthma and on the modulation of viral infection-induced airway inflammation.

Nitrogen dioxide exposure: effects on airway and blood cells

2002 ◽  
Vol 282 (1) ◽  
pp. L155-L165 ◽  
Author(s):  
Mark W. Frampton ◽  
Joseph Boscia ◽  
Norbert J. Roberts ◽  
Mitra Azadniv ◽  
Alfonso Torres ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nitrogen Dioxide ◽  
Airway Inflammation ◽  
Blood Cells ◽  
Respiratory Viruses ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Air Exposure ◽  
Syncytial Virus

This study examined the effects of nitrogen dioxide (NO2) exposure on airway inflammation, blood cells, and antiviral respiratory defense. Twenty-one healthy volunteers were exposed on separate occasions to air and 0.6 and 1.5 ppm NO2for 3 h with intermittent moderate exercise. Phlebotomy and bronchoscopy were performed 3.5 h after each exposure, and recovered cells were challenged with respiratory viruses in vitro. Blood studies revealed a 4.1% NO2dose-related decrease in hematocrit ( P = 0.003). Circulating total lymphocytes ( P = 0.024) and T lymphocytes ( P = 0.049) decreased with NO2exposure. Exposure to NO2increased the blood lymphocyte CD4+-to-CD8+ratio from 1.74 ± 0.11 to 1.85 ± 0.12 in males but decreased it from 1.88 ± 0.19 to 1.78 ± 0.19 in females ( P < 0.001 for gender difference). Polymorphonuclear leukocytes in bronchial lavage increased with NO2exposure ( P = 0.003). Bronchial epithelial cells obtained after exposure to 1.5 ppm NO2released 40% more lactate dehydrogenase after challenge with respiratory syncytial virus than with air exposure ( P = 0.024). In healthy subjects, exposures to NO2at levels found indoors cause mild airway inflammation, effects on blood cells, and increased susceptibility of airway epithelial cells to injury from respiratory viruses.

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