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Prostaglandin E2 suppresses staphylococcal enterotoxin–induced eosinophilia- associated cellular responses dominantly through an E-prostanoid 2–mediated.

Published byΣωφρονία Μαρκόπουλος Modified over 5 years ago

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Presentation on theme: "Prostaglandin E2 suppresses staphylococcal enterotoxin–induced eosinophilia- associated cellular responses dominantly through an E-prostanoid 2–mediated."— Presentation transcript:

1 Prostaglandin E2 suppresses staphylococcal enterotoxin–induced eosinophilia- associated cellular responses dominantly through an E-prostanoid 2–mediated pathway in nasal polyps  Mitsuhiro Okano, MD, Tazuko Fujiwara, BS, Takenori Haruna, MD, Shin Kariya, MD, Seiichiro Makihara, MD, Takaya Higaki, MD, Kazunori Nishizaki, MD  Journal of Allergy and Clinical Immunology  Volume 123, Issue 4, Pages e13 (April 2009) DOI: /j.jaci Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Effect of diclofenac (DIC) on SEB-induced production of IL-5 (A), IL-13 (B), RANTES (C), and eotaxin (D) by DNPCs. The rectangle includes the range from the 25th to the 75th percentiles, the horizontal line indicates the median, and the vertical line indicates the range from the 10th to the 90th percentiles. P values were determined by using the Wilcoxon signed-rank test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Inhibition of SEB-induced IL-5 (A), IL-13 (B), and RANTES (C) production by PGE2. DNPCs were treated with diclofenac and cultured with SEB in the presence of serial concentrations of PGE2 (10−8, 10−7, 10−6, and 10−5 mol/L; gray rectangle) or DMSO as a control buffer ( %, %, 0.005%, and 0.05%; open rectangle). Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Effect of EP receptor–selective agonists on SEB-induced IL-5 (A), IL-13 (B), and RANTES (C) production by DNPCs. DNPCs were treated with diclofenac and cultured with SEB in the presence of 4 EP receptor–selective agonists (10−6 mol/L) or control buffer (0.05% DMSO). Results are expressed as a percentage of inhibition. ∗P < .05, †P < .01, and ‡P < .001 compared with the buffer control. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Effect of combined stimulation of 2 of the 4 EP receptors on SEB-induced IL-5 (A), IL-13 (B), and RANTES (C) production by DNPCs. DNPCs were treated with diclofenac and cultured with SEB in the presence of 10−6 mol/L of each EP receptor–selective agonist in combination. Results are expressed as a percentage of inhibition. P values between combinations of EP receptor–selective agonists and buffer control (0.1% DMSO) were determined by using the Wilcoxon signed-rank test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Production of RANTES in response to SEB by nasal polyp fibroblasts
Production of RANTES in response to SEB by nasal polyp fibroblasts. Nasal polyp fibroblasts (n = 10) were cultured with or without 100 ng/mL SEB. After a 72-hour incubation, culture supernatants were collected, and levels of RANTES were measured by means of ELISA. The horizontal line indicates the median. P values were determined by using the Wilcoxon signed-rank test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Effect of indomethacin on SEB-induced production of IL-5 (A), IL-13 (B), RANTES (C), and eotaxin (D) by DNPCs. DNPCs were cultured with 100 ng/mL SEB in the presence or absence of 10−5 mol/L indomethacin (IND). Control cells were treated with 0.05% DMSO. The rectangle includes the range from the 25th to the 75th percentiles, the horizontal line indicates the median, and the vertical line indicates the range from the 10th to the 90th percentiles. P values were determined by using the Wilcoxon signed-rank test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Effect of neutralization of ICAM-1 on SEB-induced cytokine production by DNPCs. DNPCs (n = 6) were stimulated with SEB in the presence or absence of diclofenac (DIC). Anti–ICAM-1 mAb or control mouse IgG1 was added into the culture. After a 72-hour incubation, culture supernatant were collected, and levels of IL-5 (A), IL-13 (B), and RANTES (C) were measured by means of ELISA. The horizontal line indicates the median. P values were determined by using the Wilcoxon signed-rank test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Effect of neutralization of HLA-DR on SEB-induced cytokine production by DNPCs. DNPCs (n = 7-8) were stimulated with SEB in the presence or absence of diclofenac (DIC). Anti–HLA-DR mAb or control mouse IgG2b was added into the culture. After a 72-hour incubation, culture supernatants were collected, and levels of IL-5 (A), IL-13 (B), and RANTES (C) were measured by means of ELISA. The horizontal line indicates the median. P values were determined by using the Wilcoxon signed-rank test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Relationship between the effect of diclofenac treatment on SEB-induced IL-5 (A and D), IL-13 (B and E), and RANTES (C and F) production and the number of infiltrating eosinophils in nasal polyps (Fig E5, A-C) or the radiologic severity of sinusitis (Fig E5, D-F). Changes in the productions were calculated by means of subtraction of the production without diclofenac treatment from that with diclofenac treatment. CT, Computed tomography. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

11 Effect of PGE2 on SEB-induced IL-5 (A), IL-13 (B), and RANTES (C) production in the absence of diclofenac. Diclofenac-untreated DNPCs were cultured with SEB in the presence of serial concentrations of PGE2 or DMSO as a control buffer. After a 72-hour incubation, culture supernatants were collected, and the levels of cytokines were measured by means of ELISA. The horizontal line indicates the median. P values were determined by using the Wilcoxon signed-rank test. C, Control; E, PGE2. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

12 Production of PGE2 by DNPCs in the presence or absence of diclofenac
Production of PGE2 by DNPCs in the presence or absence of diclofenac. DNPCs (n = 9) were cultured with or without diclofenac. After a 72-hour incubation, culture supernatants were collected, and the levels of PGE2 were measured by means of ELISA. The horizontal line indicates the median. P values were determined by using the Wilcoxon signed-rank test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

13 Effect of EP receptor–selective agonists on SEB-induced IL-5 (A), IL-13 (B), and RANTES (C) production in the absence of diclofenac. Diclofenac-untreated DNPCs were cultured with SEB in the presence of 4 EP receptor–selective agonists (10−6 mol/L) or control buffer (0.05% DMSO). After a 72-hour incubation, culture supernatants were collected, and the levels of cytokines were measured by means of ELISA. Results were expressed as a percentage of inhibition calculated as follows: [1−(Concentrationwithagonist/Concentrationwithoutagonist)]×100. The horizontal line indicates the median. P values were determined by using the Wilcoxon signed-rank test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

14 Immunohistochemical staining of EP1, EP2, EP3, and EP4 protein in nasal polyps. Sections were reacted with rabbit polyclonal antibody against EP1 (A), EP2 (B), EP3 (C), and EP4 (D) or control rabbit IgG (E, under trypsin treatment; F, under autoclave treatment), after which they were stained with a Histofine MAX-PO with a diaminobenzidine substrate. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

15 Effect of SEB on EP receptor number among DNPCs
Effect of SEB on EP receptor number among DNPCs. DNPCs (n = 10) were cultured in the presence or absence of 100 ng/mL SEB for 12 hours. Relative amounts of EP1, EP2, EP3, and EP4 mRNA among DNPCs were estimated by using real-time quantitative PCR. The horizontal line indicates the median. P values were determined by using the Wilcoxon signed-rank test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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