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Cytokine milieu modulates release of thymic stromal lymphopoietin from human keratinocytes stimulated with double-stranded RNA.
J Allergy Clin Immunol. 2009 Jan; 123(1):179-86.JA

Abstract

BACKGROUND

Thymic stromal lymphopoietin (TSLP) plays a key role in allergic diseases, such as atopic dermatitis (AD) and asthma. TSLP is highly expressed by keratinocytes in skin lesions of patients with AD, but environmental triggers for its release from keratinocytes with endogenous factors are not well understood. Patients with AD, in whom allergic sensitization is already established, are susceptible to viral dissemination.

OBJECTIVES

We investigated TSLP's release from primary human keratinocytes stimulated with a Toll-like receptor (TLR) 3 ligand, polyinosinic-polycytidylic acid, which mimics viral double-stranded RNA (dsRNA), and its modulation by cytokines.

METHODS

Primary human keratinocytes were stimulated with TLR ligands, cytokines, or both. TSLP released into culture supernatants was measured by means of ELISA.

RESULTS

Stimulation of keratinocytes with dsRNA induced release of TSLP and upregulated gene expression of TSLP and other cytokines and chemokines. The release of TSLP was enhanced by the addition of IL-4, IL-13, and/or TNF-alpha. With or without the T(H)2/TNF cytokines, the dsRNA-induced release of TSLP was upregulated by IFN-alpha and IFN-beta and suppressed by IFN-gamma, TGF-beta, or IL-17.

CONCLUSIONS

The effect of the TLR3 ligand on keratinocytes suggests contribution of viral dsRNA to skin inflammations under the influence of a cytokine milieu. The results imply that viral dsRNA and a T(H)2 cytokine milieu might promote T(H)2-type inflammation through an induction of TSLP expression, suggesting that a vicious cycle exists between AD with T(H)2-type inflammation and viral infections and a possible blockade of this cycle by other cytokine milieus provided by cells, such as T(H)1, regulatory T, and T(H)17 cells.

Authors+Show Affiliations

Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19056108

Citation

Kinoshita, Hirokazu, et al. "Cytokine Milieu Modulates Release of Thymic Stromal Lymphopoietin From Human Keratinocytes Stimulated With Double-stranded RNA." The Journal of Allergy and Clinical Immunology, vol. 123, no. 1, 2009, pp. 179-86.
Kinoshita H, Takai T, Le TA, et al. Cytokine milieu modulates release of thymic stromal lymphopoietin from human keratinocytes stimulated with double-stranded RNA. J Allergy Clin Immunol. 2009;123(1):179-86.
Kinoshita, H., Takai, T., Le, T. A., Kamijo, S., Wang, X. L., Ushio, H., Hara, M., Kawasaki, J., Vu, A. T., Ogawa, T., Gunawan, H., Ikeda, S., Okumura, K., & Ogawa, H. (2009). Cytokine milieu modulates release of thymic stromal lymphopoietin from human keratinocytes stimulated with double-stranded RNA. The Journal of Allergy and Clinical Immunology, 123(1), 179-86. https://doi.org/10.1016/j.jaci.2008.10.008
Kinoshita H, et al. Cytokine Milieu Modulates Release of Thymic Stromal Lymphopoietin From Human Keratinocytes Stimulated With Double-stranded RNA. J Allergy Clin Immunol. 2009;123(1):179-86. PubMed PMID: 19056108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytokine milieu modulates release of thymic stromal lymphopoietin from human keratinocytes stimulated with double-stranded RNA. AU - Kinoshita,Hirokazu, AU - Takai,Toshiro, AU - Le,Tuan Anh, AU - Kamijo,Seiji, AU - Wang,Xiao Ling, AU - Ushio,Hiroko, AU - Hara,Mutsuko, AU - Kawasaki,Junko, AU - Vu,Anh Tuan, AU - Ogawa,Takasuke, AU - Gunawan,Hendra, AU - Ikeda,Shigaku, AU - Okumura,Ko, AU - Ogawa,Hideoki, Y1 - 2008/12/03/ PY - 2008/03/10/received PY - 2008/09/29/revised PY - 2008/10/07/accepted PY - 2008/12/6/pubmed PY - 2009/1/28/medline PY - 2008/12/6/entrez SP - 179 EP - 86 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 123 IS - 1 N2 - BACKGROUND: Thymic stromal lymphopoietin (TSLP) plays a key role in allergic diseases, such as atopic dermatitis (AD) and asthma. TSLP is highly expressed by keratinocytes in skin lesions of patients with AD, but environmental triggers for its release from keratinocytes with endogenous factors are not well understood. Patients with AD, in whom allergic sensitization is already established, are susceptible to viral dissemination. OBJECTIVES: We investigated TSLP's release from primary human keratinocytes stimulated with a Toll-like receptor (TLR) 3 ligand, polyinosinic-polycytidylic acid, which mimics viral double-stranded RNA (dsRNA), and its modulation by cytokines. METHODS: Primary human keratinocytes were stimulated with TLR ligands, cytokines, or both. TSLP released into culture supernatants was measured by means of ELISA. RESULTS: Stimulation of keratinocytes with dsRNA induced release of TSLP and upregulated gene expression of TSLP and other cytokines and chemokines. The release of TSLP was enhanced by the addition of IL-4, IL-13, and/or TNF-alpha. With or without the T(H)2/TNF cytokines, the dsRNA-induced release of TSLP was upregulated by IFN-alpha and IFN-beta and suppressed by IFN-gamma, TGF-beta, or IL-17. CONCLUSIONS: The effect of the TLR3 ligand on keratinocytes suggests contribution of viral dsRNA to skin inflammations under the influence of a cytokine milieu. The results imply that viral dsRNA and a T(H)2 cytokine milieu might promote T(H)2-type inflammation through an induction of TSLP expression, suggesting that a vicious cycle exists between AD with T(H)2-type inflammation and viral infections and a possible blockade of this cycle by other cytokine milieus provided by cells, such as T(H)1, regulatory T, and T(H)17 cells. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/19056108/Cytokine_milieu_modulates_release_of_thymic_stromal_lymphopoietin_from_human_keratinocytes_stimulated_with_double_stranded_RNA_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(08)01848-4 DB - PRIME DP - Unbound Medicine ER -