Regulatory mechanisms of Th2 cytokine–induced eotaxin-3 production in bronchial epithelial cells: possible role of interleukin 4 receptor and nuclear factor–κB

Kobayashi, Ikuko; Yamamoto, Shuichi; Nishi, Natsuko; Tsuji, Kosuke; Imayoshi, Miyoko; Inada, Shigeyasu; Ichiamaru, Tomohiro; Hamasaki, Yuhei

doi:10.1016/s1081-1206(10)61399-3

Cited by 28 publications

(24 citation statements)

References 33 publications

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“…Similar differences in the reactivity of paired cultures of human nasal and bronchial epithelial cells were also observed by other authors [26,29]. We confirmed the earlier observations of many authors that CCL26 was the main eotaxin detected in cultures of human bronchial epithelial cells stimulated with IL-4 or IL-13 [30,31]. Some of the PCR and ELISA results for CCL26 expression are inconsistent.…”

Section: Discussionsupporting

confidence: 89%

The expression of the eotaxins IL-6 and CXCL8 in human epithelial cells from various levels of the respiratory tract

Paplińska-Goryca

Nejman-Gryz

Chazan

et al. 2013

Cellular and Molecular Biology Letters

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Airway epithelium acts as multifunctional site of response in the respiratory tract. Epithelial activity plays an important part in the pathophysiology of obstructive lung disease. In this study, we compare normal human epithelial cells from various levels of the respiratory tract in terms of their reactivity to pro-allergic and pro-inflammatory stimulation. Normal human nasal, bronchial and small airway epithelial cells were stimulated with IL-4 and IL-13. The expressions of the eotaxins IL-6 and CXCL8 were evaluated at the mRNA and protein levels. The effects of pre-treatment with IFN-γ on the cell reactivity were measured, and the responses to TNF-α, LPS and IFN-γ were evaluated. All of the studied primary cells expressed CCL26, IL-6 and IL-8 after IL-4 or IL-13 stimulation. IFN-γ pre-treatment resulted in decreased CCL26 and increased IL-6 expression in the nasal and small airway cells, but this effect was not observed in the bronchial cells. IL-6 and CXCL8 were produced in varying degrees by all of the epithelial primary cells in cultures stimulated with TNF-α, LPS or IFN-γ. We showed that epithelial cells from the various levels of the respiratory tract act in a united way, responding in a similar manner to stimulation with IL-4 and IL-13, showing similar reactivity to TNF-α and LPS, and giving an almost unified response to IFN-γ pre-stimulation.

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Section: Discussionsupporting

confidence: 89%

The expression of the eotaxins IL-6 and CXCL8 in human epithelial cells from various levels of the respiratory tract

Paplińska-Goryca

Nejman-Gryz

Chazan

et al. 2013

Cellular and Molecular Biology Letters

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“…BAL fluid obtained from asthmatics is enriched in both IL-4 (50) and IL-13 (21,22) but not IFN-␥ (50), indicating the presence of T helper type 2 (Th2) subclass CD4 ϩ cells. Both IL-4 and IL-13 may stimulate epithelial cells to produce chemokines such as eotaxin-3 (28,55,65), GM-CSF (42), 28), and RANTES (17,46) and growth factors such as transforming growth factor-␤ (TGF-␤) (50,57) and the EGF receptor-binding factor, TGF-␣ (4). Overexpression of either IL-4 or IL-13 in murine airways elicits inflammation, subepithelial fibrosis, and mucous cell metaplasia (49,67).…”

mentioning

confidence: 99%

Expression of IL-4/IL-13 receptors in differentiating human airway epithelial cells

White

Martin

Stern

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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and IL-13 elicit several important responses in airway epithelium including chemokine secretion and mucous secretion that may contribute to airway inflammation, cell migration, and differentiation. These cytokines have overlapping but not identical effector profiles likely due to shared subunits in their receptor complexes. These receptors are variably described in epithelial cells, and the relative expression, localization, and function of these receptors in differentiated and repairing epithelial cells are not clear. We examined IL-4/IL-13 receptor expression and localization in primary airway epithelial cells collected from normal human lungs and grown under conditions yielding both undifferentiated and differentiated cells inclusive of basal, goblet, and ciliated cell phenotypes. Gene expression of the IL-4R␣, IL-2R␥c, IL-13R␣1, and IL-13R␣2 receptor subunits increased with differentiation, but different patterns of localization and protein abundance were seen for each subunit based on both differentiation and the cell subtypes present. Increased expression of receptor subunits observed in more differentiated cells was associated with more substantial functional responses to IL-4 stimulation including increased eotaxin-3 expression and accelerated migration after injury. We demonstrate substantial differences in IL-4/IL-13 receptor subunit expression and responsiveness to IL-4 based on the extent of airway epithelial cell differentiation and suggest that these differences may have functional consequences in airway inflammation.interleukin-4; interleukin-13; eotaxin-3; migration THE AIRWAY EPITHELIUM is both a target of inflammatory and physical insults and an effector of ongoing airway inflammation (2,20,31,37,45). As such, it plays a critical role in diseases such as chronic asthma. Epithelial injury leads to release of chemokines such as 8,13), GM-CSF (13, 42), and eotaxin (65) that then stimulate inflammatory cell infiltration. Injury also leads to disordered regulation of submucosal myofibroblasts (19) and subsequent subbasement membrane fibrinogenesis (40). Persistent epithelial injury (31,39,56) is a characteristic part of airway remodeling (9) in asthma.Activated lymphocytes are a prominent feature in asthmatic airways (5,6,32). BAL fluid obtained from asthmatics is enriched in both IL-4 (50) and IL-13 (21, 22) but not IFN-␥ (50), indicating the presence of T helper type 2 (Th2) subclass CD4 ϩ cells. Both IL-4 and IL-13 may stimulate epithelial cells to produce chemokines such as eotaxin-3 (28, 55, 65), GM-CSF (42), 28), and RANTES (17,46) and growth factors such as transforming growth factor-␤ (TGF-␤) (50, 57) and the EGF receptor-binding factor, TGF-␣ (4). Overexpression of either IL-4 or IL-13 in murine airways elicits inflammation, subepithelial fibrosis, and mucous cell metaplasia (49, 67).IL-4 and IL-13 have overlapping but not identical effector profiles likely due to shared subunits in their receptor complexes (43). IL-4 can bind to two distinct receptors: the type I receptor consisting of the...

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“…Airway epithelial cells express two types of IL-4 receptors, type 1 and type 2 IL-4Rs [17,20,29]. To the current authors' knowledge, this is the first study to report that the transfection of dsRNA enhances the expression of IL-4Ra and IL-2Rc, components of type 1 IL-4R, in airway epithelial cells.…”

Section: Discussionmentioning

confidence: 76%

“…Primary cultured normal human bronchial epithelial (NHBE) cells were obtained from Clonetics (Walkersville, MD, USA). Both cells were cultured as previously described [17].…”

Section: Cellsmentioning

confidence: 99%

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dsRNA enhances eotaxin-3 production through interleukin-4 receptor upregulation in airway epithelial cells

Tsuji

Yamamoto²,

Wei-lin³

et al. 2005

Eur Respir J

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The exacerbation of asthma during viral infections is mainly explained by neutrophils infiltrating into the airways. However, enhanced functions of eosinophils are also observed. The aim of this study was to reveal the mechanism of how eosinophils are activated during and after viral infection of the airways, using a model of viral infection.A synthetic double-stranded RNA, poly inosinic-cytidyric acid (poly(IC)), was transfected to a human airway epithelial cell line (BEAS-2B) and the primary bronchial epithelial cells, to mimic a viral infection. The production of chemokines from the cells was investigated.The transfection of poly(IC), alone, marginally affected the eotaxin-3 production of the cells. However, the transfection of poly(IC) prior to interleukin (IL)-4 stimulation enhanced eotaxin-3 production. Poly(IC) transfection increased mRNA and protein expressions of IL-4 receptor (R)a and IL-2Rc, components of the IL-4R. In BEAS-2B cells, IL-4-mediated phosphorylation of signal transducer and activator of transcription six was enhanced in poly(IC) transfected cells. This was reversed by the addition of anti-IL-4Ra antibody, suggesting the role of an increased number of IL-4 receptors in enhanced IL-4-induced eotaxin-3 production. Poly(IC)-induced upregulation of IL4Ra was inhibited by treatment with cycloheximide or dexamethasone.In conclusion, these results suggest that viral airway infection may enhance interleukin-4-induced eotaxin-3 production through upregulation of the interleukin-4 receptor in airway epithelial cells.

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Regulatory mechanisms of Th2 cytokine–induced eotaxin-3 production in bronchial epithelial cells: possible role of interleukin 4 receptor and nuclear factor–κB

Cited by 28 publications

References 33 publications

The expression of the eotaxins IL-6 and CXCL8 in human epithelial cells from various levels of the respiratory tract

The expression of the eotaxins IL-6 and CXCL8 in human epithelial cells from various levels of the respiratory tract

Expression of IL-4/IL-13 receptors in differentiating human airway epithelial cells

dsRNA enhances eotaxin-3 production through interleukin-4 receptor upregulation in airway epithelial cells

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