scholarly journals Lycopene Inhibits Toll-Like Receptor 4-Mediated Expression of Inflammatory Cytokines in House Dust Mite-Stimulated Respiratory Epithelial Cells

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3127
Author(s):  
Jiyeon Choi ◽  
Joo Weon Lim ◽  
Hyeyoung Kim
Keyword(s):  
Epithelial Cells ◽  
A549 Cells ◽  
Cytokine Expression ◽  
Ros Production ◽  
Toll Like Receptor ◽  
Respiratory Epithelial Cells ◽  
Toll Like Receptor 4 ◽  
Mitochondrial Ros ◽  
Tlr4 Activation ◽  
Respiratory Epithelial

House dust mites (HDM) are critical factors in airway inflammation. They activate respiratory epithelial cells to produce reactive oxygen species (ROS) and activate Toll-like receptor 4 (TLR4). ROS induce the expression of inflammatory cytokines in respiratory epithelial cells. Lycopene is a potent antioxidant nutrient with anti-inflammatory activity. The present study aimed to investigate whether HDM induce intracellular and mitochondrial ROS production, TLR4 activation, and pro-inflammatory cytokine expression (IL-6 and IL-8) in respiratory epithelial A549 cells. Additionally, we examined whether lycopene inhibits HDM-induced alterations in A549 cells. The treatment of A549 cells with HDM activated TLR4, induced the expression of IL-6 and IL-8, and increased intracellular and mitochondrial ROS levels. TAK242, a TLR4 inhibitor, suppressed both HDM-induced ROS production and cytokine expression. Furthermore, lycopene inhibited the HDM-induced TLR4 activation and cytokine expression, along with reducing the intracellular and mitochondrial ROS levels in HDM-treated cells. These results collectively indicated that the HDM induced TLR4 activation and increased intracellular and mitochondrial ROS levels, thus resulting in the induction of cytokine expression in respiratory epithelial cells. The antioxidant lycopene could inhibit HDM-induced cytokine expression, possibly by suppressing TLR4 activation and reducing the intracellular and mitochondrial ROS levels in respiratory epithelial cells.

scholarly journals Differential Role of CbpA and PspA in Modulation of In Vitro CXC Chemokine Responses of Respiratory Epithelial Cells to Infection with Streptococcus pneumoniae

2006 ◽  
Vol 74 (12) ◽  
pp. 6739-6749 ◽  
Author(s):  
Rikki M. A. Graham ◽  
James C. Paton
Keyword(s):  
Streptococcus Pneumoniae ◽  
Epithelial Cells ◽  
Deletion Mutant ◽  
Protein A ◽  
A549 Cells ◽  
Respiratory Pathogens ◽  
Respiratory Epithelial Cells ◽  
Cxc Chemokine ◽  
Respiratory Epithelial

ABSTRACTRespiratory epithelial cells play an active part in the host response to respiratory pathogens, such asStreptococcus pneumoniae, by releasing chemokines responsible for neutrophil recruitment. In order to investigate the role of specific pneumococcal virulence factors in eliciting CXC chemokine responses, type II pneumocytes (A549) and nasopharyngeal cells (Detroit-562) were infected withS. pneumoniaeD39 or mutants lacking choline-binding protein A (CbpA), pneumococcal surface protein A (PspA), or specific domains thereof. In response to wild-type D39, both A549 and Detroit-562 cells showed a significant increase in CXC chemokine mRNA and interleukin-8 protein. This response was increased twofold when acbpAdeletion mutant (ΔCbpA) was used, suggesting that CbpA inhibits CXC chemokine induction. All three N-terminal domains of CbpA are required for this effect, as in-frame deletion of the respective region ofcbpAhad the same effect on the CXC chemokine response as deletion ofcbpAaltogether. Infection with apspAdeletion mutant (ΔPspA) led to a twofold decrease in the CXC chemokine response of A549 but not Detroit-562 cells, compared to infection with D39 at 2 h. Thus, PspA appears to have the ability to stimulate early CXC chemokine release from A549 cells. Deletion of the region ofpspAencoding the first N-terminal α-helical domain reduced the ability ofS. pneumoniaeto elicit a chemokine response to the same degree as deletion ofpspAaltogether. Thus, the N termini of CbpA and PspA exert differential effects on CXC chemokine induction in epithelial cells infected withS. pneumoniae.

scholarly journals Whey protein hydrolysates decrease IL-8 secretion in lipopolysaccharide (LPS)-stimulated respiratory epithelial cells by affecting LPS binding to Toll-like receptor 4

2013 ◽  
Vol 110 (1) ◽  
pp. 58-68 ◽  
Author(s):  
Michèle M. Iskandar ◽  
Nurlan Dauletbaev ◽  
Stan Kubow ◽  
Nadir Mawji ◽  
Larry C. Lands
Keyword(s):  
Epithelial Cells ◽  
Antioxidant Capacity ◽  
Cell Lines ◽  
Inflammatory Responses ◽  
Clinical Effects ◽  
Toll Like Receptor ◽  
Respiratory Epithelial Cells ◽  
Anti Inflammatory ◽  
Respiratory Epithelial ◽  
Lps Binding

Whey proteins (WP) exert anti-inflammatory and antioxidant effects. Hyperbaric pressurisation of whey increases its digestibility and changes the spectrum of peptides released during digestion. We have shown that dietary supplementation with pressurised whey improves nutritional status and systemic inflammation in patients with cystic fibrosis (CF). Both clinical indices are largely affected by airway processes, to which respiratory epithelial cells actively contribute. Here, we tested whether peptides released from the digestion of pressurised whey can attenuate the inflammatory responses of CF respiratory epithelial cells. Hydrolysates of pressurised WP (pWP) and native WP (nWP, control) were generatedin vitroand tested for anti-inflammatory properties judged by the suppression of IL-8 production in CF and non-CF respiratory epithelial cell lines (CFTE29o- and 1HAEo-, respectively). We observed that, in both cell lines, pWP hydrolysate suppressed IL-8 production stimulated by lipopolysaccharide (LPS) to a greater magnitude compared with nWP hydrolysate. Neither hydrolysate suppressed IL-8 production induced by TNF-α or IL-1β, suggesting an effect on the Toll-like receptor (TLR) 4 pathway, the cellular sensor for LPS. Further, neither hydrolysate affected TLR4 expression or neutralised LPS. Both pWP and nWP hydrolysates similarly reduced LPS binding to surface TLR4, while pWP tended to more potently increase extracellular antioxidant capacity. In conclusion: (1) anti-inflammatory properties of whey are enhanced by pressurisation; (2) suppression of IL-8 production may contribute to the clinical effects of pressurised whey supplementation on CF; (3) this effect may be partly explained by a combination of reduced LPS binding to TLR4 and enhanced extracellular antioxidant capacity.

scholarly journals Fimbria-Mediated Enhanced Attachment of NontypeableHaemophilus influenzae to Respiratory Syncytial Virus-Infected Respiratory Epithelial Cells

1999 ◽  
Vol 67 (1) ◽  
pp. 187-192 ◽  
Author(s):  
Zili Jiang ◽  
Nobuo Nagata ◽  
Edgar Molina ◽  
Lauren O. Bakaletz ◽  
Hal Hawkins ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
A549 Cells ◽  
Respiratory Epithelial Cells ◽  
Nthi Strain ◽  
Soluble Mediator ◽  
Isogenic Mutant Strain ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Respiratory Epithelial

ABSTRACT Respiratory syncytial virus (RSV) infection is known to predispose children to otitis media and sinusitis due to bacteria such as nontypeable Haemophilus influenzae (NTHI). In this study, we investigated the role of NTHI surface outer membrane protein P5-homologous fimbriae (P5-fimbriae) in attachment to RSV-exposed A549 epithelial cells. Analysis by fluorescence flow cytometry showed that a live P5-fimbriated NTHI strain (NTHIF+) attached to a higher proportion of RSV-exposed A549 cells than to control cells (mean, 68% for RSV versus 29% for control; P = 0.008), while attachment of the P5-fimbriae-deficient isogenic mutant strain (NTHIF−) was significantly lower than in control cells and rose only slightly following RSV exposure (mean, 17% for RSV versus 10% for control, P = 0.229). Attachment of NTHIF+ did not correlate with the amount of RSV antigen expressed by A549 cells. Furthermore, paraformaldehyde-fixed NTHIF+ also demonstrated an enhanced binding to RSV-exposed cells. Observations by transmission electronic microscopy showed that the mean number of bacteria attached per 100 RSV-exposed A549 cells was higher for NTHIF+ than NTHIF− (99 versus 18; P < 0.001). No intracellular bacteria were identified. UV-irradiated conditioned supernatants collected from RSV-infected A549 cultures (UV-cRSV) also enhanced the attachment of NTHIF+ to A549, suggesting the presence of a preformed soluble mediator(s) in UV-cRSV that enhances the expression of receptors for P5-fimbriae on A549 cells. In summary, RSV infection significantly enhances NTHI attachment to respiratory epithelial cells. P5-fimbria is the critical appendage of NTHI that participates in this attachment. In clinical settings, blocking of the P5-fimbria-mediated attachment of NTHIF+ by passive or active immunity may reduce the morbidity due to NTHI during RSV infection.

scholarly journals Naegleria fowleri induces MUC5AC and pro-inflammatory cytokines in human epithelial cells via ROS production and EGFR activation

Microbiology ◽  
2009 ◽  
Vol 155 (11) ◽  
pp. 3739-3747 ◽  
Author(s):  
Isaac Cervantes-Sandoval ◽  
José de Jesús Serrano-Luna ◽  
Patricia Meza-Cervantez ◽  
Rossana Arroyo ◽  
Víctor Tsutsumi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Mediators ◽  
Interleukin 1 ◽  
Growth Factor Receptor ◽  
Ros Production ◽  
Naegleria Fowleri ◽  
Respiratory Epithelial Cells ◽  
Egfr Activation ◽  
Nægleria Fowleri ◽  
Respiratory Epithelial

Naegleria fowleri is an amoeboflagellate responsible for the fatal central nervous system (CNS) disease primary amoebic meningoencephalitis (PAM). This amoeba gains access to the CNS by invading the olfactory mucosa and crossing the cribriform plate. Studies using a mouse model of infection have shown that the host secretes mucus during the very early stages of infection, and this event is followed by an infiltration of neutrophils into the nasal cavity. In this study, we investigated the role of N. fowleri trophozoites in inducing the expression and secretion of airway mucin and pro-inflammatory mediators. Using the human mucoepidermal cell line NCI-H292, we demonstrated that N. fowleri induced the expression of the MUC5AC gene and protein and the pro-inflammatory mediators interleukin-8 (IL-8) and interleukin-1β (IL-1β), but not tumour necrosis factor-α or chemokine c-c motif ligand 11 (eotaxin). Since the production of reactive oxygen species (ROS) is a common phenomenon involved in the signalling pathways of these molecules, we analysed if trophozoites were capable of causing ROS production in NCI-H292 cells by detecting oxidation of the fluorescent probe 2,7-dichlorofluorescein diacetate. NCI-H292 cells generated ROS after 15–30 min of trophozoite stimulation. Furthermore, the expression of MUC5AC, IL-8 and IL-1β was inhibited in the presence of the ROS scavenger DMSO. In addition, the use of an epidermal growth factor receptor inhibitor decreased the expression of MUC5AC and IL-8, but not IL-1β. We conclude that N. fowleri induces the expression of some host innate defence mechanisms, such as mucin secretion (MUC5AC) and local inflammation (IL-8 and IL-1β) in respiratory epithelial cells via ROS production and suggest that these innate immune mechanisms probably prevent most PAM infections.

scholarly journals Role of Flagella in Host Cell Invasion by Burkholderia cepacia

2002 ◽  
Vol 70 (4) ◽  
pp. 1799-1806 ◽  
Author(s):  
Mladen Tomich ◽  
Christine A. Herfst ◽  
Joseph W. Golden ◽  
Christian D. Mohr
Keyword(s):  
Epithelial Cells ◽  
Burkholderia Cepacia ◽  
Protein Translocation ◽  
A549 Cells ◽  
Systemic Infection ◽  
Respiratory Epithelial Cells ◽  
Isolation And Characterization ◽  
Systemic Spread ◽  
Epithelial Barriers ◽  
Respiratory Epithelial

ABSTRACT Burkholderia cepacia is an important opportunistic human pathogen that affects immunocompromised individuals, particularly cystic fibrosis (CF) patients. Colonization of the lungs of a CF patient by B. cepacia can lead not only to a decline in respiratory function but also to an acute systemic infection, such as bacteremia. We have previously demonstrated that a CF clinical isolate of B. cepacia, strain J2315, can invade and survive within cultured respiratory epithelial cells. In order to further characterize the mechanisms of invasion of B. cepacia, we screened a transposon-generated mutant library of strain J2315 for mutants defective in invasion of A549 respiratory epithelial cells. Here we describe isolation and characterization of a nonmotile mutant of B. cepacia with reduced invasiveness due to disruption of fliG, which encodes a component of the motor-switch complex of the flagellar basal body. We also found that a defined null mutation in fliI, a gene encoding a highly conserved ATPase required for protein translocation via the flagellar type III secretion system, also resulted in loss of motility and a significant reduction in invasion. Both mutants lacked detectable intracellular flagellin and failed to export detectable amounts of flagellin into culture supernatants, suggesting that disruption of fliG and fliI impaired flagellar biogenesis. The reduction in invasion did not appear to be due to defective adherence of the flagellar mutants to A549 cells, suggesting that functional flagella and motility are required for full invasiveness of B. cepacia. Our findings indicate that flagellum-mediated motility may facilitate penetration of host epithelial barriers by B. cepacia, contributing to establishment of infection and systemic spread of the organism.

scholarly journals Cytokine Responses to Group B Streptococci Induce Nitric Oxide Production in Respiratory Epithelial Cells

2002 ◽  
Vol 70 (1) ◽  
pp. 49-54 ◽  
Author(s):  
Kenneth J. Goodrum ◽  
Jane Poulson-Dunlap
Keyword(s):  
Nitric Oxide ◽  
Epithelial Cells ◽  
Culture Medium ◽  
Mononuclear Cells ◽  
A549 Cells ◽  
Inos Mrna ◽  
Respiratory Epithelial Cells ◽  
Human Mononuclear Cells ◽  
Group B ◽  
Respiratory Epithelial

ABSTRACT Streptococcus agalactiae (group B streptococcus [GBS]) is a leading cause of neonatal pneumonia, sepsis, and meningitis. Early-onset GBS pneumonia is characterized by marked pulmonary epithelial and endothelial cell injury. Innate proinflammatory responses to GBS infection that may contribute to the respiratory pathology include the synthesis and release of cytokines, prostaglandins, and nitric oxide (NO). The hypothesis that NO is directly induced in lung epithelial cells by invading GBS or indirectly induced by cytokines released by GBS-infected mononuclear cells was tested. A549 transformed human respiratory epithelial cells were directly cultured with GBS, cocultured with GBS-infected human mononuclear cells or purified macrophages, or exposed to conditioned culture medium from human mononuclear cells infected by GBS. The culture medium of A549 cultures was assayed for NO secretion, and the cell lysates were tested for presence of inducible nitric oxide synthase (iNOS) mRNA by reverse transcriptase PCR (RT-PCR). GBS-treated A549 cells neither secreted detectable NO nor expressed iNOS mRNA. GBS interaction with human mononuclear cells, however, stimulated release of soluble factors that readily induced iNOS mRNA expression and NO secretion by A549 cells. Inflammatory mediator-induced nitric oxide (NO) production by alveolar epithelium may exceed that of other lung cell types such as macrophages, and induction during GBS infection may play a significant role in pulmonary defense or free-radical-mediated lung injury.

scholarly journals Early Bacterial Colonization Induces Toll-Like Receptor-Dependent Transforming Growth Factor β Signaling in the Epithelium

2009 ◽  
Vol 77 (5) ◽  
pp. 2212-2220 ◽  
Author(s):  
Christoph Beisswenger ◽  
Elena S. Lysenko ◽  
Jeffrey N. Weiser
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Epithelial Barrier ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Respiratory Epithelial Cells ◽  
Mucosal Barrier Function ◽  
Respiratory Epithelial

ABSTRACT Colonization of the upper respiratory tract is an initial step that may lead to disease for many pathogens. To prevent compromise of the epithelial barrier, the host must monitor and tightly control bacterial levels on the mucosa. Here we show that innate immune functions of respiratory epithelial cells control colonization by Streptococcus pneumoniae and Haemophilus influenzae in a Toll-like receptor (TLR)-dependent manner. Activation of inflammatory pathways, including mitogen-activated protein kinase signaling, in respiratory epithelial cells was accompanied by the induction of the transforming growth factor β signaling cascade during early colonization. Thus, colonization resulted in upregulation of factors involved in a proinflammatory response (e.g., interleukin-6) as well as factors known to modulate the epithelial barrier (e.g., Snail-1). These in vivo data provided a link between inflammation control and maintenance of the mucosal barrier function during infection and emphasized the importance of TLR-dependent inflammatory responses of the respiratory epithelium.

scholarly journals Synergistic Upregulation of Interleukin-8 Secretion from Pulmonary Epithelial Cells by Direct and Monocyte-Dependent Effects of Respiratory Syncytial Virus Infection

2000 ◽  
Vol 74 (18) ◽  
pp. 8425-8433 ◽  
Author(s):  
Lynette H. Thomas ◽  
Melissa I. Y. Wickremasinghe ◽  
Mike Sharland ◽  
Jon S. Friedland
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
A549 Cells ◽  
Interleukin 8 ◽  
Respiratory Epithelial Cells ◽  
Necrosis Factor Alpha ◽  
Leukocyte Influx ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Respiratory Epithelial

ABSTRACT Respiratory syncytial virus (RSV) infection is the major cause of severe bronchiolitis in infants. Pathology of this infection is partly due to excessive proinflammatory leukocyte influx mediated by chemokines. Although direct infection of the respiratory epithelium by RSV may induce chemokine secretion, little is known about the role of cytokine networks. We investigated the effects of conditioned medium (CM) from RSV-infected monocytes (RSV-CM) on respiratory epithelial (A549) cell chemokine release. RSV-CM, but not control CM (both at a 1:5 dilution), stimulated interleukin-8 (IL-8) secretion from A549 cells within 2 h, and secretion increased over 72 h to 11,360 ± 1,090 pg/ml without affecting cell viability. In contrast, RSV-CM had only a small effect on RANTES secretion. RSV-CM interacted with direct RSV infection to synergistically amplify IL-8 secretion from respiratory epithelial cells (levels of secretion at 48 h were as follows: RSV-CM alone, 8,140 ± 2,160 pg/ml; RSV alone, 12,170 ± 300 pg/ml; RSV-CM plus RSV, 27,040 ± 5,260 pg/ml; P < 0.05). RSV-CM induced degradation of IκBα within 5 min but did not affect IκBβ. RSV-CM activated transient nuclear binding of NF-κB within 1 h, while activation of NF-IL6 was delayed until 8 h and was still detectable at 24 h. Promoter-reporter analysis demonstrated that NF-κB binding was essential and that NF-IL6 was important for IL-8 promoter activity in RSV-CM-activated cells. Blocking experiments revealed that the effects of RSV-CM depended on monocyte-derived IL-1 but that tumor necrosis factor alpha was not involved in this network. In summary, RSV infection of monocytes results in and amplifies direct RSV-mediated IL-8 secretion from respiratory epithelial cells by an NF-κB-dependent, NF-IL6-requiring mechanism.

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