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Histamine receptor 2 is a key influence in immune responses to intestinal histamine- secreting microbes Ruth Ferstl, PhD, Remo Frei, PhD, Elisa Schiavi, PhD, Patrycja Konieczna, PhD, Weronika Barcik, MSc, Mario Ziegler, Dipl-Ing, Roger P. Lauener, MD, Christophe Chassard, PhD, Christophe Lacroix, PhD, Cezmi A. Akdis, MD, Liam O'Mahony, PhD Journal of Allergy and Clinical Immunology Volume 134, Issue 3, Pages e3 (September 2014) DOI: /j.jaci Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 1 Histamine from Lactobacillus saerimneri 30a is biologically active. A, L saerimneri 30a culture supernatants significantly reduced LPS-induced NF-κB activation, which was attenuated by blocking the H2R with famotidine. Supernatant from Lactobacillus reuteri (which does not secrete histamine) increased LPS-induced NF-κB activation. *P < .05 compared with LPS alone. Results are expressed as mean ± SD for 3 separate experiments. B, HPLC analysis revealed high levels of histamine and cadaverine in supernatants from L saerimneri 30a cultures. Journal of Allergy and Clinical Immunology , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 2 Lactobacillus saerimneri 30a modulates mucosal immune responses via the H2R. Mice (n = 6 per group) received L saerimneri 30a daily for 6 days by oral gavage (1 × 109 cfu/mL). Animals exhibited significant weight loss (A) associated with signs of deteriorating health (B), which was significantly worse in the H2R-deficient animals than in wild-type controls at day 6 (*P < .05 between groups). C, In vitro cytokine secretion from resected PPs was measured after PMA and ionomycin stimulation. L saerimneri 30a administration was associated with the suppression of IL-17 and IFN-γ secretion in wild-type mice. In contrast, IL-4, IL-6, and IL-17 secretion was significantly increased in H2R-deficient animals (*P < .05; **P < .01). PMA, Phorbol 12-myristate 13-acetate. Journal of Allergy and Clinical Immunology , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig E1 The H2R antagonist famotidine enhances the detrimental effects of L saerimneri 30a. Mice (n = 8 per group) received L saerimneri 30a daily for 6 days by oral gavage (1 × 109 cfu/mL). Animals exhibited significant weight loss (A) associated with signs of deteriorating health (B), which was significantly worse in the famotidine-treated animals than in controls (*P < .05 between groups). C, In vitro cytokine secretion from mucosal cells was measured after PMA and ionomycin stimulation. L saerimneri 30a administration was associated with the suppression of IL-17; however, the secretion of IL-17 was enhanced in famotidine-treated animals. PMA, Phorbol 12-myristate 13-acetate. Journal of Allergy and Clinical Immunology , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig E2 CD4+ lymphocyte cytokine response to L saerimneri 30a. Intracellular staining of IL-17+ and IFN-γ+ CD4 lymphocytes was performed for PP (A) and mesenteric lymph nodes (B). The percentage of IL-17+ lymphocytes within the PP decreased after the administration of L saerimneri to both wild-type and H2R-deficient animals, while no significant differences were observed in the mesenteric lymph nodes. A nonstatistically significant trend toward reduced IFN-γ+ lymphocytes after the administration of L saerimneri 30a was observed only in PP cells isolated from wild-type animals (n = 6 per group, *P < .05). Journal of Allergy and Clinical Immunology , e3DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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