Cytokine milieu modulates release of thymic stromal lymphopoietin from human keratinocytes stimulated with double-stranded RNA Hirokazu Kinoshita, MD,

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Presentation transcript:

Cytokine milieu modulates release of thymic stromal lymphopoietin from human keratinocytes stimulated with double-stranded RNA Hirokazu Kinoshita, MD, Toshiro Takai, PhD, Tuan Anh Le, MD, Seiji Kamijo, PhD, Xiao Ling Wang, MD, Hiroko Ushio, DVM, PhD, Mutsuko Hara, BSc, Junko Kawasaki, MD, Anh Tuan Vu, MD, Takasuke Ogawa, MD, Hendra Gunawan, MD, PhD, Shigaku Ikeda, MD, PhD, Ko Okumura, MD, PhD, Hideoki Ogawa, MD, PhD Journal of Allergy and Clinical Immunology Volume 123, Issue 1, Pages 179-186 (January 2009) DOI: 10.1016/j.jaci.2008.10.008 Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Poly I:C induced release of TSLP from keratinocytes: A, TSLP; B, IL-8. Broken line, Less than the minimum detection limit. PGN, Peptidoglycan. C, Expression of TSLP mRNA at 3 hours after stimulation was analyzed by means of quantitative real-time PCR and is presented as fold change relative to medium. ∗P < .05 versus medium by means of ANOVA (Fig 1, A and B) and t test (Fig 1, C). Journal of Allergy and Clinical Immunology 2009 123, 179-186DOI: (10.1016/j.jaci.2008.10.008) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Poly I:C induced upregulation of gene expression of TSLP and other cytokines and chemokines in keratinocytes. Expression of mRNA at 4 and 8 hours after stimulation was analyzed by means of quantitative real-time PCR and is presented as fold change relative to medium at 4 hours. Data shown are representative of 3 independent experiments. MIG, Monokine induced by IFN-γ; IP-10, IFN-inducible protein 10; I-TAC, IFN-inducible T-cell α chemoattractant; MCP-1, monocyte chemoattractant protein 1; MIP-3α, macrophage inflammatory protein 3α; MDC, macrophage-derived chemokine. Journal of Allergy and Clinical Immunology 2009 123, 179-186DOI: (10.1016/j.jaci.2008.10.008) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Time course and dose dependency of poly I:C–induced release of TSLP from keratinocytes in the absence or presence of TH2/TNF cytokines: A-C, TSLP; D-F, IL-8. nd, Less than the minimum detection limit (broken line). ∗P < .05 versus without poly I:C by means of ANOVA. #P < .05 and $P < .05 versus without TH2/TNF cytokines by means of t test. Journal of Allergy and Clinical Immunology 2009 123, 179-186DOI: (10.1016/j.jaci.2008.10.008) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 TNF-α and TH2 cytokines synergistically upregulated poly I:C–induced release of TSLP from keratinocytes: A-C, TSLP; D-F, IL-8. nd, Less than the minimum detection limit (broken line). ∗P < .05 versus without the TH2/TNF cytokines by means of ANOVA. #P < .05 versus without poly I:C by means of the t test. Journal of Allergy and Clinical Immunology 2009 123, 179-186DOI: (10.1016/j.jaci.2008.10.008) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Type I IFNs upregulated poly I:C–induced release of TSLP from keratinocytes: A-C, TSLP; D-F, IL-8. nd, Less than the minimum detection limit (broken line). ∗P < .05 versus without the type I IFNs by means of ANOVA. #P < .05 versus without the TH2/TNF cytokines and $P < .05 versus without poly I:C by means of the t test. Journal of Allergy and Clinical Immunology 2009 123, 179-186DOI: (10.1016/j.jaci.2008.10.008) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 IFN-γ, TGF-β, and IL-17 suppressed poly I:C–induced release of TSLP from keratinocytes: A-C, TSLP; D-F, IL-8. nd, Less than the minimum detection limit (broken line). ∗P < .05 versus the control by means of ANOVA. Journal of Allergy and Clinical Immunology 2009 123, 179-186DOI: (10.1016/j.jaci.2008.10.008) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions