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Breast Milk Cytokines and Maternal Allergy
Abstracts AB129
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
Inhibition Of Chemokine Secretion From Stimulated Airway Smooth Muscle (asm) By Glucocorticoids And Vitamin D Requires Vitamin D Receptor (vdr) Activation A. Banerjee, H. Fogle, R. A. Panettieri, Jr, ; University of Pennsylvania, Philadelphia, PA. RATIONALE: 1, 25 dihydroxyvitamin D3 alone and in combination with glucocorticoids inhibits chemokine synthesis from cytokine-stimulated ASM cells. Here we postulate that VDR activation is necessary to mediate vitamin D effects on chemokine secretion from human ASM cells. METHODS: Human Tracheal ASM cells were transfected with VDR shRNA and treated with calcitriol (10-1000nm) and/or dexamethasone (10-1000nm) then stimulated with TNFa. RANTES and IL-8 secretion were assayed by ELISA. Untransfected cells and cells transfected with scrambled RNA served as controls. RESULTS: Stimulation with TNFa induces RANTES and IL-8 secretion in ASM. While treatment with either dexamethasone or calcitriol inhibits RANTES secretion in untransfected cells or cells transfected with scrambled RNA, inhibition of RANTES secretion by dexamethasone or calcitriol treatment was diminished in ASM cells transfected with VDR shRNA and stimulated with TNFa. Conversely, inhibition of IL-8 secretion in TNFa stimulated ASM cells treated with dexamethasone was unaffected by transfection of VDR shRNA. CONCLUSIONS: The inhibition of RANTES secretion from stimulated ASM by glucocorticoid and vitamin D requires, in part, VDR activation, while glucocorticoid inhibits IL-8 secretion from stimulated ASM independent of the VDR. These data suggest that vitamin D selectively modulates structural cell secretion of chemokines and synergizes with glucocorticoids to control inflammation.
488
Breast Milk Cytokines and Maternal Allergy J. L. Burch, N. Soto-Ramirez, W. Karmaus; University of South Carolina, Columbia, SC. RATIONALE: Maternal allergy is considered a predisposition for allergic disease in offspring; cytokine levels in breast milk may confer a risk for infant allergy. We investigated whether cytokine levels in breast milk are influenced by maternal allergy controlling for other factors such as smoking. METHODS: Mature milk was obtained approximately two weeks after delivery (n5105) and separated into fat and whey. Using the Bioplex analyzer, interferon (IFN)-g, interferon gamma-induced protein 10 (IP-10 or CXCL10), eotaxin, interleukin (IL) 1b, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-13 levels were measured in duplicate. Maternal history of allergy (asthma, eczema, rhinitis), smoking, pet exposure, education, and race, and offspring sex were ascertained by telephone interviews. To normalize the data, cytokine levels were log transformed. General linear models were used to estimate the effect of maternal allergy on cytokine levels, adjusting for confounders. RESULTS: Any maternal allergies were associated with lower levels of IL-6 in breast milk (p50.01). A history of allergic rhinitis was linked to decreased levels of IL-8 (p50.03) and lower levels of IL-13 (p50.02). Maternal smoking during pregnancy was related to increased levels of IFN-g (p50.001), eotaxin (p50.02), IL-4 (p50.013), and IL-6 (p50.04). Pet ownership was not associated with breast milk cytokine levels. African American women had higher IL-6 levels (p50.0001) compared to Caucasians. CONCLUSIONS: Maternal allergy, with the exception of rhinitis, did not have a major effect on cytokine levels in breast milk. To our knowledge, no study - when assessing maternal allergy - controlled for smoking, which may affect breast milk cytokine levels.
489
Involvement of Interleukin-17 in Oxazolone-induced Allergic Contact Dermatitis in Mice J. Hong, M. Kim, K. Lee, K. Kim, M. Sohn; Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 Project for Medical science, Yonsei University College of Medicine, Seoul, KOREA, REPUBLIC OF. RATIONALE: Allergic contact dermatitis (ACD) is very similar to atopic dermatitis in clinical, histological and immunological aspect. It has reported that Interleukin (IL)-17, one of T cell derived cytokines is detected in AD and psoriasis. In this study, we made mouse models with oxazolone (oxa)-induced ACD and investigated whether IL-17 affects inflammatory responses of oxa-challenged ACD mice. METHODS: Wild type (wt) and IL-17 knock-out (ko) mice (balb/c) were used for oxa-induced ACD (oxa-ACD) model. Mice were sensitized on their flank with 500 mg oxa (day 0) and challenged on their ears with 100 mg oxa (day 7). Control group was treated with only ethanol instead of oxa. After measuring ear thickness, ears were collected for mRNA synthesis and histological analysis. RESULTS: Ear thickness relatively increased in both wt and IL-17 ko mice with oxa-ACD over control mice. On H&E stained ear epidermises and mRNA of IL-4, 13, 17, oxa-ACD mice showed distinctively increased cell infiltration and those cytokine expressions, whereas oxa-ACD IL-17 ko mice did not. CONCLUSION: We concluded that IL-17 might play a crucial role in inflammation triggered by oxa-induced ACD mice model.
SUNDAY
487
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
Inhibition Of Chemokine Secretion From Stimulated Airway Smooth Muscle (asm) By Glucocorticoids And Vitamin D Requires Vitamin D Receptor (vdr) Activation A. Banerjee, H. Fogle, R. A. Panettieri, Jr, ; University of Pennsylvania, Philadelphia, PA. RATIONALE: 1, 25 dihydroxyvitamin D3 alone and in combination with glucocorticoids inhibits chemokine synthesis from cytokine-stimulated ASM cells. Here we postulate that VDR activation is necessary to mediate vitamin D effects on chemokine secretion from human ASM cells. METHODS: Human Tracheal ASM cells were transfected with VDR shRNA and treated with calcitriol (10-1000nm) and/or dexamethasone (10-1000nm) then stimulated with TNFa. RANTES and IL-8 secretion were assayed by ELISA. Untransfected cells and cells transfected with scrambled RNA served as controls. RESULTS: Stimulation with TNFa induces RANTES and IL-8 secretion in ASM. While treatment with either dexamethasone or calcitriol inhibits RANTES secretion in untransfected cells or cells transfected with scrambled RNA, inhibition of RANTES secretion by dexamethasone or calcitriol treatment was diminished in ASM cells transfected with VDR shRNA and stimulated with TNFa. Conversely, inhibition of IL-8 secretion in TNFa stimulated ASM cells treated with dexamethasone was unaffected by transfection of VDR shRNA. CONCLUSIONS: The inhibition of RANTES secretion from stimulated ASM by glucocorticoid and vitamin D requires, in part, VDR activation, while glucocorticoid inhibits IL-8 secretion from stimulated ASM independent of the VDR. These data suggest that vitamin D selectively modulates structural cell secretion of chemokines and synergizes with glucocorticoids to control inflammation.
488
Breast Milk Cytokines and Maternal Allergy J. L. Burch, N. Soto-Ramirez, W. Karmaus; University of South Carolina, Columbia, SC. RATIONALE: Maternal allergy is considered a predisposition for allergic disease in offspring; cytokine levels in breast milk may confer a risk for infant allergy. We investigated whether cytokine levels in breast milk are influenced by maternal allergy controlling for other factors such as smoking. METHODS: Mature milk was obtained approximately two weeks after delivery (n5105) and separated into fat and whey. Using the Bioplex analyzer, interferon (IFN)-g, interferon gamma-induced protein 10 (IP-10 or CXCL10), eotaxin, interleukin (IL) 1b, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-13 levels were measured in duplicate. Maternal history of allergy (asthma, eczema, rhinitis), smoking, pet exposure, education, and race, and offspring sex were ascertained by telephone interviews. To normalize the data, cytokine levels were log transformed. General linear models were used to estimate the effect of maternal allergy on cytokine levels, adjusting for confounders. RESULTS: Any maternal allergies were associated with lower levels of IL-6 in breast milk (p50.01). A history of allergic rhinitis was linked to decreased levels of IL-8 (p50.03) and lower levels of IL-13 (p50.02). Maternal smoking during pregnancy was related to increased levels of IFN-g (p50.001), eotaxin (p50.02), IL-4 (p50.013), and IL-6 (p50.04). Pet ownership was not associated with breast milk cytokine levels. African American women had higher IL-6 levels (p50.0001) compared to Caucasians. CONCLUSIONS: Maternal allergy, with the exception of rhinitis, did not have a major effect on cytokine levels in breast milk. To our knowledge, no study - when assessing maternal allergy - controlled for smoking, which may affect breast milk cytokine levels.
489
Involvement of Interleukin-17 in Oxazolone-induced Allergic Contact Dermatitis in Mice J. Hong, M. Kim, K. Lee, K. Kim, M. Sohn; Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 Project for Medical science, Yonsei University College of Medicine, Seoul, KOREA, REPUBLIC OF. RATIONALE: Allergic contact dermatitis (ACD) is very similar to atopic dermatitis in clinical, histological and immunological aspect. It has reported that Interleukin (IL)-17, one of T cell derived cytokines is detected in AD and psoriasis. In this study, we made mouse models with oxazolone (oxa)-induced ACD and investigated whether IL-17 affects inflammatory responses of oxa-challenged ACD mice. METHODS: Wild type (wt) and IL-17 knock-out (ko) mice (balb/c) were used for oxa-induced ACD (oxa-ACD) model. Mice were sensitized on their flank with 500 mg oxa (day 0) and challenged on their ears with 100 mg oxa (day 7). Control group was treated with only ethanol instead of oxa. After measuring ear thickness, ears were collected for mRNA synthesis and histological analysis. RESULTS: Ear thickness relatively increased in both wt and IL-17 ko mice with oxa-ACD over control mice. On H&E stained ear epidermises and mRNA of IL-4, 13, 17, oxa-ACD mice showed distinctively increased cell infiltration and those cytokine expressions, whereas oxa-ACD IL-17 ko mice did not. CONCLUSION: We concluded that IL-17 might play a crucial role in inflammation triggered by oxa-induced ACD mice model.
SUNDAY
487