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

Tsuji, Kosuke; Yamamoto, Shuichi; Wei-lin, OU; Nishi, Natsuko; Kobayashi, Ikuko; Zaitsu, Masafumi; Muro, Eriko; Sadakane, Yutaka; Ichimaru, Tomohiro; Hamasaki, Yuhei

doi:10.1183/09031936.05.00010805

Cited by 22 publications

(19 citation statements)

References 32 publications

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“…TSLP-activated DC express OX40L and promote the differentiation of TNF-␣-producing inflammatory Th2 cells from naive T cells (24). In addition, TLR3 activation strongly induced eosinophil-recruiting chemokines in the presence of Th2 cytokines (51,52). Together, these findings suggest that viral infection in a Th2 environment may amplify allergic reactions locally.…”

Section: Discussionmentioning

confidence: 52%

“…Enhancement of CCL26 by the combination of IL-4 and dsRNA was found to be a secondary effect of the induction of the IL-4 receptor by dsRNA in airway epithelial cells (52). In the present study of TSLP expression, dsRNA and IL-4 stimulated NHBE rapidly (Fig.…”

Section: Discussionmentioning

confidence: 65%

“…It has been reported that dsRNA and IL-4 synergistically enhanced the production of the eosinophil-recruiting chemokines CCL11 and CCL26 (eotaxin-3) in airway smooth muscle cells and airway epithelial cells, respectively (51,52). Enhancement of CCL26 by the combination of IL-4 and dsRNA was found to be a secondary effect of the induction of the IL-4 receptor by dsRNA in airway epithelial cells (52).…”

Section: Discussionmentioning

confidence: 99%

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TLR3- and Th2 Cytokine-Dependent Production of Thymic Stromal Lymphopoietin in Human Airway Epithelial Cells

Kato

Favoreto

Avila

et al. 2007

The Journal of Immunology

443

424

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Thymic stromal lymphopoietin (TSLP) is elevated in asthma and triggers dendritic cell-mediated activation of Th2 inflammatory responses. Although TSLP has been shown to be produced mainly by airway epithelial cells, the regulation of epithelial TSLP expression has not been extensively studied. We investigated the expression of TSLP in cytokine- or TLR ligand-treated normal human bronchial epithelial cells (NHBE). The mRNA for TSLP was significantly up-regulated by stimulation with IL-4 (5.5-fold) and IL-13 (5.3-fold), weakly up-regulated by TNF-α, TGF-β, and IFN-β, and not affected by IFN-γ in NHBE. TSLP mRNA was only significantly up-regulated by the TLR3 ligand (dsRNA) among the TLR ligands tested (66.8-fold). TSLP was also induced by in vitro infection with rhinovirus. TSLP protein was detected after stimulation with dsRNA (120 ± 23 pg/ml). The combination of TNF-α and IL-4 produced detectable levels of TSLP protein (40 ± 13 pg/ml). In addition, TSLP was synergistically enhanced by a combination of IL-4 and dsRNA (mRNA; 207-fold, protein; 325 ± 75 pg/ml). The induction of TSLP by dsRNA was dependent upon NF-κB and IFN regulatory factor 3 (IRF-3) signaling via TLR3 as indicated by a study with small interfering RNA. The potent topical glucocorticoid fluticasone propionate significantly suppressed dsRNA-dependent TSLP production in NHBE. These results suggest that the expression of TSLP is induced in airway epithelial cells by stimulation with the TLR3 ligand and Th2 cytokines and that this response is suppressed by glucocorticoid treatment. This implies that respiratory viral infection and the recruitment of Th2 cytokine producing cells may amplify Th2 inflammation via the induction of TSLP in the asthmatic airway.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

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TLR3- and Th2 Cytokine-Dependent Production of Thymic Stromal Lymphopoietin in Human Airway Epithelial Cells

Kato

Favoreto

Avila

et al. 2007

The Journal of Immunology

443

424

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“…Previous studies have shown that poly(I:C) or virus-derived dsRNA increases the production of cytokines and chemokines, including IL-6, CCL5, CXCL8, and CXCL10 in primary cultures or immortalized bronchial epithelial cells, such as BEAS2B (15)(16)(17)(18)(19)(20). In the present study, we have confirmed that poly(I:C) is also a potent stimulant of the synthesis of CCL5 in BSMC, as well as of IL-6, CXCL8, and CXCL10.…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that dsRNA, as a virus genome fragment or as a replicative intermediate of RNA virus (14), induces the production of chemokines, such as CCL5, MCP-1/CCL2, eotaxin-3/CCL26, IL-8/CXCL8, and IFN-inducible protein-10/ CXCL10 in respiratory epithelial cells (15)(16)(17)(18)(19)(20). TLR3, a receptor for dsRNA, is expressed in respiratory epithelial cells, as well as in dendritic cells, mast cells, and fibroblasts (21)(22)(23).…”

Section: Tlr3-mediated Synthesis and Release Of Eotaxin-1/ccl11 From mentioning

confidence: 99%

TLR3-Mediated Synthesis and Release of Eotaxin-1/CCL11 from Human Bronchial Smooth Muscle Cells Stimulated with Double-Stranded RNA

Niimi

Asano

Shiraishi

et al. 2007

The Journal of Immunology

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Respiratory infections with RNA viruses, such as rhinovirus or respiratory syncytial virus, are a major cause of asthma exacerbation, accompanied by enhanced neutrophilic and/or eosinophilic inflammation of the airways. We studied the effects of dsRNA synthesized during RNA virus replication, and of its receptor, TLR3, on the synthesis of eosinophilic chemokines in bronchial smooth muscle cells (BSMC). Synthetic dsRNA, polyinosinic-cystidic acid (poly(I:C)), induced the synthesis of eosinophilic chemokines, eotaxin-1/CCL11 and RANTES/CCL5, from primary cultures of human BSMC, and IL-4 increased synergistically the synthesis of poly(I:C)-induced CCL11. A robust eosinophil chemotactic activity was released from BSMC stimulated with poly(I:C) and IL-4, which was mostly inhibited by preincubation with an anti-CCL11, but not with an anti-CCL5 Ab. Although the immunoreactivity of TLR3 was detectable on the cellular surface of BSMC by flow cytometric analysis, pretreatment with an anti-TLR3-neutralizing Ab failed to block the poly(I:C)-induced synthesis of CCL11. We have determined by confocal laser-scanning microscopy that the immunoreactivity of TLR3 was aggregated intracellularly in poly(I:C)-stimulated BSMC, colocalizing with fluorescein-labeled poly(I:C). The synthesis of CCL11 was prominently inhibited by the transfection of TLR3-specific small interfering RNA or by bafilomycin A1, an endosomal acidification inhibitor, further supporting the essential role played by intracellular TLR3 in the synthesis of poly(I:C)-induced CCL11 in BSMC. In conclusion, these observations suggest that, by activating intracellular TLR3 in BSMC, respiratory RNA virus infections stimulate the production of CCL11 and enhance eosinophilic inflammation of the airways in the Th2-dominant microenvironment.

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Combined Stimulation of Nasal Polyp Fibroblasts With Poly IC, Interleukin 4, and Tumor Necrosis Factor α Potently Induces Production of Thymus- and Activation-Regulated Chemokine

Nonaka

Ogihara²,

Fukumoto³

et al. 2008

Arch Otolaryngol Head Neck Surg

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

Cited by 22 publications

References 32 publications

TLR3- and Th2 Cytokine-Dependent Production of Thymic Stromal Lymphopoietin in Human Airway Epithelial Cells

TLR3- and Th2 Cytokine-Dependent Production of Thymic Stromal Lymphopoietin in Human Airway Epithelial Cells

TLR3-Mediated Synthesis and Release of Eotaxin-1/CCL11 from Human Bronchial Smooth Muscle Cells Stimulated with Double-Stranded RNA

Combined Stimulation of Nasal Polyp Fibroblasts With Poly IC, Interleukin 4, and Tumor Necrosis Factor α Potently Induces Production of Thymus- and Activation-Regulated Chemokine

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