title: Prostaglandins E2 signal mediated by receptor subtype EP2 promotes IgE production in vivo and contributes to asthma development.
abstract: Prostaglandins E2 (PGE2) has been shown to enhance IgE production by B cells in vitro. The physiological and pathological relevance of this phenomenon and the underlying molecular mechanism, however, remain to be elucidated. B cells from wild type and EP2-deficient mice were compared in culture for their responses to PGE2 in terms of IgE class switching and production. Ovalbumin (OVA)-induced asthma models were used to evaluate the impact of EP2-deficiency on IgE responses and the development of asthma. PGE2 promoted IgE class switching, generation of IgE(+) cells and secretion of IgE by B cells stimulated with LPS+IL4. These effects were much attenuated as a consequence of EP2 deficiency. Consistent with the in vitro data, EP2-deficient mice showed a markedly suppressed IgE antibody response and developed less pronounced airway inflammation in the OVA-induced asthma model. Mechanistic studies demonstrated that PGE2, in an EP2-depedent manner, enhanced STAT6 activation induced by IL-4, thereby promoting the expression of IgE germline and post switch transcripts and the transcription of activation-induced cytidine deaminase (AID). Collectively, these data support an important regulatory role of the PGE2-EP2-STAT6 signaling pathway in IgE response and allergic diseases.
authors: Department of Immunology, and Key Laboratory of Medical Immunology of Ministry of Public Health, Peking University Health Science Center, Beijing, China.
authors: Yuhan
authors: Y
authors: Gao
authors: Department of Immunology, and Key Laboratory of Medical Immunology of Ministry of Public Health, Peking University Health Science Center, Beijing, China.
authors: Chunyan
authors: C
authors: Zhao
authors: Department of Immunology, and Key Laboratory of Medical Immunology of Ministry of Public Health, Peking University Health Science Center, Beijing, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Immunology, and Key Laboratory of Medical Immunology of Ministry of Public Health, Peking University Health Science Center, Beijing, China.
authors: Rong
authors: R
authors: Jin
authors: Department of Immunology, and Key Laboratory of Medical Immunology of Ministry of Public Health, Peking University Health Science Center, Beijing, China.
authors: Qian
authors: Q
authors: Li
authors: Department of Immunology, and Key Laboratory of Medical Immunology of Ministry of Public Health, Peking University Health Science Center, Beijing, China.
authors: Qing
authors: Q
authors: Ge
authors: Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China.
authors: Youfei
authors: Y
authors: Guan
authors: Department of Immunology, and Key Laboratory of Medical Immunology of Ministry of Public Health, Peking University Health Science Center, Beijing, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
authors: Yu
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000032:analysis / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D017455:Receptors, IgE; D058307:Receptors, Prostaglandin E, EP2 Subtype; D050800:STAT6 Transcription Factor; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin; D003564:Cytidine Deaminase; D015232:Dinoprostone