The Primary Role in Biologic Activity of the Neutrophil Chemokines IL-8 and GRO-αin Cultured Nasal Epithelial Cells

Rudack, Claudia; Maune, Steffen; Eble, Johannes A.; Schroeder, Johann O.

doi:10.1089/107999003321455507

Cited by 32 publications

(26 citation statements)

References 36 publications

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“…The medium was exchanged by serum-free medium 24 h prior to stimulation. The epithelial phenotype of cells was confirmed by staining of epithelial cells with a monoclonal anti-pan cytokeratin antibody as previously shown [13]. A549 cells (ATTC CCL-185) were obtained from the American Type Culture Collection (Manassas, Va., USA) and cultivated as described previously [14].…”

Section: Methodsmentioning

confidence: 99%

Proinflammatory Impact of Staphylococcus epidermidis on the Nasal Epithelium Quantified by IL-8 and GRO-α Responses in Primary Human Nasal Epithelial Cells

Sachse¹,

Eiff²,

Becker³

et al. 2007

Int Arch Allergy Immunol

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Background: Bacterial etiology of chronic rhinosinusitis (CRS) still remains controversial. Whereas Staphylococcus aureus enterotoxins have been detected in CRS, the impact of Staphylococcus epidermidis, a major commensal inhabitant of the nose, has not been studied. Among others, serine and cysteine proteases have been identified as factors of virulence in S. epidermidis. Methods:S. epidermidis was examined in tissue biopsies of 30 CRS patients (16 with nasal polyposis) using standard procedures. Primary human nasal epithelial cells from inferior nasal turbinates (HNECs), from nasal polyps (NPECs) and A549 airway epithelial cells were stimulated with S. epidermidis supernatants DSM20044 or ATCC35984 and the IL-8 and GRO-α response was quanti- fied by ELISA. Protease-triggered chemokine responses and involvement of NF-ĸB were investigated by addition of protease or NF-ĸB inhibitors. Activation of NF-ĸB was demonstrated by quantitative DNA binding assay. Results:S. epidermidis was the most frequently isolated bacteria in the majority of CRS patients. HNECs and NPECs revealed no different IL-6 and IL-8 synthesis following stimulation with DSM20044 or ATCC35984. Stimulation of HNECs and A549 cells with S. epidermidis supernatants resulted in increased IL-8 and GRO-α expression which could be suppressed by the serine protease inhibitor AEBSF and the NF-ĸB inhibitor BAY 11 but not by the cysteine protease inhibitor E64. Results obtained for A549 cells were similar to HNECs. Conclusion:S. epidermidis was present in the majority of CRS specimens. Proinflammatory impact of S. epidermidis supernatants on nasal epithelial cells was demonstrated by serine protease-triggered and NF-ĸB-dependent chemokine responses.

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Section: Methodsmentioning

confidence: 99%

Proinflammatory Impact of Staphylococcus epidermidis on the Nasal Epithelium Quantified by IL-8 and GRO-α Responses in Primary Human Nasal Epithelial Cells

Sachse¹,

Eiff²,

Becker³

et al. 2007

Int Arch Allergy Immunol

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“…The tissue was washed with PBS and incubated with trypsin (0.5%) overnight at 4°C, as previously described, with minor modifications (13). Cells were grown to confluence (ϳ2 wk) and passaged two further times before they were used for experiments.…”

Section: Primary Nasal Epithelial Cell Culture From Turbinate Mucosa mentioning

confidence: 99%

Immunomodulation of Nasal Epithelial Cells by Staphylococcus aureus-Derived Serine Proteases

Rudack

Sachse²,

Albert³

et al. 2009

The Journal of Immunology

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The impact of Staphylococcus aureus in the pathogenesis of chronic rhinosinusitis is not well understood. Therefore, we investigated primary human nasal epithelial cell cultures for their ability to produce IL-8, growth-related oncogene-α, and IL-6 via stimulation with trypsin and culture supernatants of different S. aureus strains and phenotypes. Inhibition of cytokine synthesis was performed using a glucocorticoid, a serine protease inhibitor, and a cysteine protease inhibitor. Finally, signal transduction pathways were analyzed by quantifying phosphorylated forms of MAPKs (PI3K, ERK, and p38) and DNA-binding assays that quantified NF-κB and its inhibition using BAY11-7085. In vitro studies showed that the induction of IL-8, growth-related oncogene-α, and IL-6 by S. aureus culture supernatants was significantly inhibited by the serine protease inhibitor. In contrast, steroids and the cysteine protease inhibitor had little effect. Activation of NF-κB was observed after cell treatment with trypsin and bacterial supernatants, and was inhibited by BAY11-7085 and the serine protease inhibitor. S. aureus serine proteases were identified to modulate chemokine synthesis and activate NF-κB in nasal epithelial cells, and may therefore be relevant for the pathophysiology of chronic rhinosinusitis.

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“…In addition to GROs, this family also comprises epithelium-derived neutrophilactivating peptide 78 (CXCL5), granulocyte chemotactic protein 2 (CXCL6), neutrophil-activating peptide 2 (CXCL7), and IL-8 (CXCL8) (8,9). CXCL1, CXCL2, and CXCL3 are well known as powerful neutrophil chemoattractants (10) and are involved in cancer metastasis (11), angiogenesis, and wound healing (12). Recently, GROs have been postulated to play a role in asthma severity (13,14) and asthmatic airway remodeling (7,15).…”

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confidence: 99%

Differential Roles of CXCL2 and CXCL3 and Their Receptors in Regulating Normal and Asthmatic Airway Smooth Muscle Cell Migration

Al-Alwan

Chang

Mogas

et al. 2013

The Journal of Immunology

105

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Structural cell migration plays a central role in the pathophysiology of several diseases, including asthma. Previously, we established that IL-17–induced (CXCL1, CXCL2, and CXCL3) production promoted airway smooth muscle cell (ASMC) migration, and consequently we sought to investigate the molecular mechanism of CXC-induced ASMC migration. Recombinant human CXCL1, CXCL2, and CXCL3 were used to assess migration of human primary ASMCs from normal and asthmatic subjects using a modified Boyden chamber. Neutralizing Abs or small interfering RNA (siRNA) knockdown and pharmacological inhibitors of PI3K, ERK1/2, and p38 MAPK pathways were used to investigate the receptors and the signaling pathways involved in CXC-induced ASMC migration, respectively. We established the ability of CXCL2 and CXCL3, but not CXCL1, to induce ASMC migration at the tested concentrations using normal ASMCs. We found CXCL2-induced ASMC migration to be dependent on p38 MAPK and CXCR2, whereas CXCL3-induced migration was dependent on p38 and ERK1/2 MAPK pathways via CXCR1 and CXCR2. While investigating the effect of CXCL2 and CXCL3 on asthmatic ASMC migration, we found that they induced greater migration of asthmatic ASMCs compared with normal ones. Interestingly, unlike normal ASMCs, CXCL2- and CXCL3-induced asthmatic ASMC migration was mainly mediated by the PI3K pathway through CXCR1. In conclusion, our results establish a new role of CXCR1 in ASMC migration and demonstrate the diverse mechanisms by which CXCL2 and CXCL3 mediate normal and asthmatic ASMC migration, suggesting that they may play a role in the pathogenesis of airway remodeling in asthma.

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The Primary Role in Biologic Activity of the Neutrophil Chemokines IL-8 and GRO-αin Cultured Nasal Epithelial Cells

Cited by 32 publications

References 36 publications

Proinflammatory Impact of <i>Staphylococcus epidermidis</i> on the Nasal Epithelium Quantified by IL-8 and GRO-α Responses in Primary Human Nasal Epithelial Cells

Proinflammatory Impact of <i>Staphylococcus epidermidis</i> on the Nasal Epithelium Quantified by IL-8 and GRO-α Responses in Primary Human Nasal Epithelial Cells

Immunomodulation of Nasal Epithelial Cells by Staphylococcus aureus-Derived Serine Proteases

Differential Roles of CXCL2 and CXCL3 and Their Receptors in Regulating Normal and Asthmatic Airway Smooth Muscle Cell Migration

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