Kou, Xiao-XingLi, Chen-ShuangHe, Dan-QingWang, Xue-DongHao, TingMeng, ZhenZhou, Yan-HengGan, Ye-Hua2023-05-222023-05-222015-03-152022-06-29https://repository.upenn.edu/handle/20.500.14332/9266Macrophages play a major role in joint inflammation. Estrogen is involved in rheumatoid arthritis and temporomandibular disorders. However, the underlying mechanism is still unclear. This study was done to verify and test how estrogen affects M1/M2-like macrophage polarization and then contributes to joint inflammation. Female rats were ovariectomized and treated with increasing doses of 17β-estradiol for 10 d and then intra-articularly injected with CFA to induce temporomandibular joint (TMJ) inflammation. The polarization of macrophages and expression of cadherin-11 was evaluated at 24 h after the induction of TMJ inflammation and after blocking cadherin-11 or estrogen receptors. NR8383 macrophages were treated with estradiol and TNF-α, with or without blocking cadherin-11 or estrogen receptors, to evaluate the expression of the M1/M2-like macrophageassociated genes. We found that estradiol increased the infiltration of macrophages with a proinflammatory M1-like predominant profile in the synovium of inflamed TMJ. In addition, estradiol dose-dependently upregulated the expressions of the M1-associated proinflammatory factor inducible NO synthase (iNOS) but repressed the expressions of the M2-associated genes IL-10 and arginase in NR8383 macrophages. Furthermore, estradiol mainly promoted cadherin-11 expression in M1-like macrophages of inflamed TMJ. By contrast, blockage of cadherin-11 concurrently reversed estradiol-potentiated M1-like macrophage activation and TMJ inflammation, as well as reversed TNF-α-induced induction of inducible NO synthase and NO in NR8383 macrophages. The blocking of estrogen receptors reversed estradiol-potentiated M1-like macrophage activation and cadherin-11 expression. These results suggested that estradiol could promote M1-like macrophage activation through cadherin-11 to aggravate the acute inflammation of TMJs. Copyright © 2015 by The American Association of Immunologists, Inc.AnimalsArginaseArthritisBlottingWesternCadherinsEstradiolEstrogen Receptor AntagonistsEstrogensFemaleGene ExpressionInflammationInterleukin-10Macrophage ActivationMacrophagesMicroscopyConfocalNitric OxideNitric Oxide Synthase Type IIOvariectomyRatsSprague-DawleyReceptorsEstrogenReverse Transcriptase Polymerase Chain ReactionTemporomandibular JointTumor Necrosis Factor-alphaarginasecadherincadherin 11estradiolestrogen receptorinducible nitric oxide synthaseinterleukin 10tumor necrosis factor alphaunclassified drugarginasecadherinestradiolestrogenestrogen receptor antagonistfulvestrantinducible nitric oxide synthaseinterleukin 10nitric oxideosteoblast cadherintumor necrosis factor alphaanimal cellanimal experimentanimal modelanimal tissuearthritisArticlecell infiltrationcontrolled studyfemalegene expressiongene repressioninflammationmacrophage activationnonhumanovariectomypolarizationpriority journalprotein expressionratreceptor blockingsynoviumtemporomandibular joint disorderanalogs and derivativesanimalantagonists and inhibitorsconfocal microscopydrug effectsgeneticsimmunologymacrophagemacrophage activationmetabolismpathologyreverse transcription polymerase chain reactionSprague Dawley rattemporomandibular jointWestern blottingDental MaterialsDentistryOral Biology and Oral PathologyPeriodontics and PeriodontologyArticle