title: Estrogen increases, whereas IL-27 and IFN-gamma decrease, splenocyte IL-17 production in WT mice.
abstract: Estrogen-mediated regulation of Th1, Th2 and Treg effector functions are well documented but, surprisingly, there is little information whether estrogen modulates IL-17, a powerful proinflammatory cytokine that plays a pivotal role in several inflammatory and autoimmune diseases. Therefore in the current study, we determined whether estrogen regulates the expression levels of IL-17 in WT C57BL/6 mice. By ELISA, ELISPOT and/or flow cytometric analyses, we found that estrogen upregulated the levels of not only IL-17, but also the IL-17-specific transcription factor retinoic acid-related orphan receptor gamma t (ROR gamma t), in activated splenocytes. IL-17 levels were further enhanced by exposure of activated splenocytes to IL-23, particularly in cells from estrogen-treated mice. Exposure of splenocytes to IL-27 or IFN-gamma at the time of activation markedly inhibited the levels of IL-17 and ROR gamma t. Interestingly, a delay of 24 h in exposure of activated splenocytes to IL-27 or IFN-gamma decreased IL-17 levels (albeit less profoundly) but not ROR gamma t. These findings imply that the suppressive effects of IL-27 and IFN-gamma are more effective prior to the differentiation and commitment of IL-17-secreting cells. Furthermore, inhibition of JAK-2 by AG490 suppressed IL-17 but not ROR gamma t expression, suggesting that other transcription factors are also critical in estrogen-mediated upregulation of IL-17.
authors.affiliation: Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060-0342, USA.
authors.forename: Deena
authors.initials: D
authors.lastname: Khan
authors.forename: Rujuan
authors.initials: R
authors.lastname: Dai
authors.forename: Ebru
authors.initials: E
authors.lastname: Karpuzoglu
authors.forename: Sattar Ansar
authors.initials: SA
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D053759:Interleukin-23 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis* / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D004967:Estrogens; C486767:Il27 protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D007371:Interferon-gamma; D053614:Janus Kinase 2