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Prostaglandin E2–EP3 signaling suppresses skin inflammation in murine contact hypersensitivity  Tetsuya Honda, MD, PhD, Toshiyuki Matsuoka, MD, PhD, Mayumi.

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Presentation on theme: "Prostaglandin E2–EP3 signaling suppresses skin inflammation in murine contact hypersensitivity  Tetsuya Honda, MD, PhD, Toshiyuki Matsuoka, MD, PhD, Mayumi."— Presentation transcript:

1 Prostaglandin E2–EP3 signaling suppresses skin inflammation in murine contact hypersensitivity 
Tetsuya Honda, MD, PhD, Toshiyuki Matsuoka, MD, PhD, Mayumi Ueta, MD, PhD, Kenji Kabashima, MD, PhD, Yoshiki Miyachi, MD, PhD, Shuh Narumiya, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 124, Issue 4, Pages e2 (October 2009) DOI: /j.jaci Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Suppressive effects of EP3 agonist on the ear-swelling response in mice with CHS. A and B, Results are expressed as means ± SEMs (n = 5 in both groups). Data are representative of 3 experiments. C, HE staining of control- and DNFB-challenged ears treated with either vehicle or EP3 agonist. Representative samples of each group are shown. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Localization of EP3 receptors and effect of topical application of EP3 agonist on mice with CHS. A, Histochemical staining for EP3 (X-gal) counterstained with HE or anti–keratin 5 antibody. Arrows, Positive signaling (blue); black arrowheads, positive staining of keratin 5; white arrowheads, colocalization of positive signals in X-gal and anti–keratin 5 staining. B, Immunohistologic analysis for EP3. The arrow indicates positive signals. C-E, Suppressive effects of topical administration of EP3 agonist and effects of various EP agonists (1 μmol/L) on murine CHS (n = 5 per group [Fig 2, C] and n = 4 per group [Fig 2, D and E]). Data are representative of 2 experiments. F, Effect of AE248 on murine CHS of bone marrow chimera (n = per group). Results are a combination of 3 independent experiments. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Microarray analysis for the effect of AE248 on gene expressions. Genes with a signal intensity that increased more than 2-fold in 24 hours at elicitation from baseline are selected (total of 902 genes). The signal intensity of each gene in the AE248-treated group (n = 3) was compared with the average signal intensity of each gene in the vehicle-treated group (n = 3), and the change ratio was indicated by means of color gradation. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Effect of AE248 on CXCL1 production and neutrophil accumulation at the elicitation site. A, Real-time RT-PCR analysis on mRNA expression of CXCL1 in the keratinocytes in hapten-challenged ears of vehicle- or AE248-treated mice (n = 3 per group). B, ELISA analysis of CXCL1 production from cultured keratinocytes (n = 3 per group). Results are expressed as means ± SEMs and are representative of 3 independent experiments. C, Number of polymorphonuclear cells in the skin (n = 4 per group). ∗P < .05 versus the vehicle-treated group. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Enhanced inflammation of indomethacin (indo)–treated mice or Ptger3−/− mice in repeated-challenge CHS. A, Effect of topical administration of indomethacin on murine CHS (n = 4 per group). B, Increased ear swelling of Ptger3−/− mice in the CHS group (n = 4 per group). ∗P < .05 versus WT mice. Data are representative of 3 independent experiments. C, Representative HE staining of ear skin in WT and Ptger3−/− mice with repeated-challenge CHS at 24 hours after the fourth challenge. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Real-time RT-PCR analysis on mRNA expression of CXCL2 in the purified keratinocytes in hapten-challenged ears of vehicle- or AE248-treated mice (n = 3 per group). Results are expressed as means ± SEMs. ∗P < .05 versus the vehicle-treated group. GAPDH, Glyceraldehyde-3-phosphate dehydrogenase. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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