Epidermal growth factor receptor reactivation induced by E-prostanoid-3 receptor- and tumor necrosis factor-alpha-converting enzyme-dependent feedback exaggerates interleukin-8 production in airway cancer (NCI-H292) cells

Kim, Suil; Lewis, Courtney; Nadel, Jay A.

doi:10.1016/j.yexcr.2011.08.023

Cited by 15 publications

(15 citation statements)

References 39 publications

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“…For stimulation purposes, NCI-H292 cells were seeded into 24-well tissue-culture plates and grown until confluence. Cell stimulations and infections were performed in free serum culture medium to maintain a low basal level of mucins, as we [37] and others [38] have recently described. Cells were suspended in the free serum culture medium without antibiotics and stimulated with different multiplicities of infection (MOI) of bacteria, as specified in the figure legends.…”

Section: Methodsmentioning

confidence: 99%

A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa

et al. 2012

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Pseudomonas aeruginosa is an opportunistic pathogen involved in nosocomial infections. Flagellin is a P. aeruginosa virulence factor involved in host response to this pathogen. We examined the role of flagellin in P. aeruginosa-induced mucus secretion. Using a mouse model of pulmonary infection we showed that PAK, a wild type strain of P. aeruginosa, induced airway mucus secretion and mucin muc5ac expression at higher levels than its flagellin-deficient mutant (ΔFliC). PAK induced expression of MUC5AC and MUC2 in both human airway epithelial NCI-H292 cell line and in primary epithelial cells. In contrast, ΔFliC infection had lower to no effect on MUC5AC and MUC2 expressions. A purified P. aeruginosa flagellin induced MUC5AC expression in parallel to IL-8 secretion in NCI-H292 cells. Accordingly, ΔFliC mutant stimulated IL-8 secretion at significantly lower levels compared to PAK. Incubation of NCI-H292 cells with exogenous IL-8 induced MUC5AC expression and pre-incubation of these cells with an anti-IL-8 antibody abrogated flagellin-mediated MUC5AC expression. Silencing of TLR5 and Naip, siRNA inhibited both flagellin-induced MUC5AC expression and IL-8 secretion. Finally, inhibition of ERK abolished the expression of both PAK- and flagellin-induced MUC5AC. We conclude that: (i) flagellin is crucial in P. aeruginosa-induced mucus hyper-secretion through TLR5 and Naip pathways; (ii) this process is mediated by ERK and amplified by IL-8. Our findings help understand the mechanisms involved in mucus secretion during pulmonary infectious disease induced by P. aeruginosa, such as in cystic fibrosis.

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Section: Methodsmentioning

confidence: 99%

A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa

et al. 2012

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“…Cells containing normal CFTR: A) Human airway epithelial (NCI-H292) cells [38], which express wild-type CFTR [32], were purchased from American Type Culture Collection (Manassas, VA), and were grown in RPMI 1640 medium containing 10% fetal bovine serum, penicillin (100 U/ml), streptomycin (100 µcg/ml), and 25 mM HEPES at 37°C in a humidified 5% CO2 water-jacketed incubator as described previously [30]. NCI-H292 cells have been shown to contain the intermediate filament protein keratin [38], confirming the epithelial origin of these cells.…”

Section: Methodsmentioning

confidence: 99%

“…Subauste and Proud first showed that treatment of airway epithelial cells with EGFR ligands results in IL-8 production [22]. Since then, multiple stimuli have been shown to induce airway epithelial IL-8 production via activation of a surface TACE-EGFR cascade [20], [21], [27]–[30], suggesting that this cascade is a convergent pathway for airway epithelial IL-8 production.…”

Section: Introductionmentioning

confidence: 99%

“…We chose the CFTR-selective inhibitor CFTR-172 [31] because CFTR-172 has been shown to induce IL-8 production in airway epithelial cells containing normal CFTR [17]–[19], and because Perez et al reported no off-target effects of CFTR-172 in airway epithelial cells containing mutant CFTR [17]. We chose human airway epithelial (NCI-H292) cells because they contain normal CFTR [32], and because these cells are a well characterized and widely used model system of IL-8 production [20], [29], [30]. Normal human bronchial epithelial (NHBE) cells were used to confirm findings described in the NCI-H292 cells.…”

Section: Introductionmentioning

confidence: 99%

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Normal CFTR Inhibits Epidermal Growth Factor Receptor-Dependent Pro-Inflammatory Chemokine Production in Human Airway Epithelial Cells

et al. 2013

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Mutations in cystic fibrosis transmembrane conductance regulator (CFTR) protein cause cystic fibrosis, a disease characterized by exaggerated airway epithelial production of the neutrophil chemokine interleukin (IL)-8, which results in exuberant neutrophilic inflammation. Because activation of an epidermal growth factor receptor (EGFR) signaling cascade induces airway epithelial IL-8 production, we hypothesized that normal CFTR suppresses EGFR-dependent IL-8 production and that loss of CFTR at the surface exaggerates IL-8 production via activation of a pro-inflammatory EGFR cascade. We examined this hypothesis in human airway epithelial (NCI-H292) cells and in normal human bronchial epithelial (NHBE) cells containing normal CFTR treated with a CFTR-selective inhibitor (CFTR-172), and in human airway epithelial (IB3) cells containing mutant CFTR versus isogenic (C38) cells containing wild-type CFTR. In NCI-H292 cells, CFTR-172 induced IL-8 production EGFR-dependently. Pretreatment with an EGFR neutralizing antibody or the metalloprotease TACE inhibitor TAPI-1, or TACE siRNA knockdown prevented CFTR-172-induced EGFR phosphorylation (EGFR-P) and IL-8 production, implicating TACE-dependent EGFR pro-ligand cleavage in these responses. Pretreatment with neutralizing antibodies to IL-1R or to IL-1alpha, but not to IL-1beta, markedly suppressed CFTR-172-induced EGFR-P and IL-8 production, suggesting that binding of IL-1alpha to IL-1R stimulates a TACE-EGFR-IL-8 cascade. Similarly, in NHBE cells, CFTR-172 increased IL-8 production EGFR-, TACE-, and IL-1alpha/IL-1R-dependently. In IB3 cells, constitutive IL-8 production was markedly increased compared to C38 cells. EGFR-P was increased in IB3 cells compared to C38 cells, and exaggerated IL-8 production in the IB3 cells was EGFR-dependent. Activation of TACE and binding of IL-1alpha to IL-1R contributed to EGFR-P and IL-8 production in IB3 cells but not in C38 cells. Thus, we conclude that normal CFTR suppresses airway epithelial IL-8 production that occurs via a stimulatory EGFR cascade, and that loss of normal CFTR activity exaggerates IL-8 production via activation of a pro-inflammatory EGFR cascade.

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“…Adjuvant chemotherapy and surgical resection are standard therapies, but treatment eicacy still remains poor for over one-third of osteosarcoma patients [5,8]. Although our understanding of the mechanisms underlying tumor development, tumor progression, and metastasis is improving [6,[9][10][11][12], the complex nature of the bone tumor microenvironment presents unique challenges to identifying novel drug targets and treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

Smeester¹,

Moriarity²,

Beitz³

2017

Osteosarcoma - Biology, Behavior and Mechanisms

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Osteosarcoma is the most common primary cancer of the bone and third most common cancer in children and adolescents with approximately 900 new cases annually in the United States. A major facet of osteosarcoma is its high level of genomic instability, in particular chromosomal instability, which is the result of increased or decreased chromosome number in a cell. Furthermore, pain is the most common symptomatic feature of osteosarcoma that lacks efective therapy. Pain in osteosarcoma is relatively more complicated than many other painful conditions requiring a more thorough understanding of its etiology, pathobiology, and neurobiology to allow the development of beter therapies for reducing pain in osteosarcoma patients. Studies are underway to deine the diverse modalities of presentation, growth, development, metastases, and nociception in osteosarcoma. New data from human studies in combination with data from studies incorporating transgenic mouse models of osteosarcoma are providing valuable insights into the mechanisms underlying the development of both the tumor and the tumor-induced pain. These new data will undoubtedly lead to improved prognoses, as well as the development of novel therapeutics that will signiicantly decrease bone cancer pain.

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Epidermal growth factor receptor reactivation induced by E-prostanoid-3 receptor- and tumor necrosis factor-alpha-converting enzyme-dependent feedback exaggerates interleukin-8 production in airway cancer (NCI-H292) cells

Cited by 15 publications

References 39 publications

A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa

A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa

Normal CFTR Inhibits Epidermal Growth Factor Receptor-Dependent Pro-Inflammatory Chemokine Production in Human Airway Epithelial Cells

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

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