Departmental Papers (Dental)
Estradiol Promotes M1-like Macrophage Activation through Cadherin-11 To Aggravate Temporomandibular Joint Inflammation in Rats
Date of this Version
Journal of Immunology
Macrophages 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.
Animals, Arginase, Arthritis, Blotting, Western, Cadherins, Estradiol, Estrogen Receptor Antagonists, Estrogens, Female, Gene Expression, Inflammation, Interleukin-10, Macrophage Activation, Macrophages, Microscopy, Confocal, Nitric Oxide, Nitric Oxide Synthase Type II, Ovariectomy, Rats, Sprague-Dawley, Receptors, Estrogen, Reverse Transcriptase Polymerase Chain Reaction, Temporomandibular Joint, Tumor Necrosis Factor-alpha, arginase, cadherin, cadherin 11, estradiol, estrogen receptor, inducible nitric oxide synthase, interleukin 10, tumor necrosis factor alpha, unclassified drug, arginase, cadherin, estradiol, estrogen, estrogen receptor antagonist, fulvestrant, inducible nitric oxide synthase, interleukin 10, nitric oxide, osteoblast cadherin, tumor necrosis factor alpha, animal cell, animal experiment, animal model, animal tissue, arthritis, Article, cell infiltration, controlled study, female, gene expression, gene repression, inflammation, macrophage activation, nonhuman, ovariectomy, polarization, priority journal, protein expression, rat, receptor blocking, synovium, temporomandibular joint disorder, analogs and derivatives, animal, antagonists and inhibitors, confocal microscopy, drug effects, genetics, immunology, macrophage, macrophage activation, metabolism, pathology, reverse transcription polymerase chain reaction, Sprague Dawley rat, temporomandibular joint, Western blotting
Kou, X., Li, C., He, D., Wang, X., Hao, T., Meng, Z., Zhou, Y., & Gan, Y. (2015). Estradiol Promotes M1-like Macrophage Activation through Cadherin-11 To Aggravate Temporomandibular Joint Inflammation in Rats. Journal of Immunology, 194 (6), 2810-2818. http://dx.doi.org/10.4049/jimmunol.1303188
Dental Materials Commons, Oral Biology and Oral Pathology Commons, Periodontics and Periodontology Commons
Date Posted: 10 February 2023
This document has been peer reviewed.
At the time of publication, author Xiao-Xing Kou was affiliated with the Hospital of Stomatology, Peking University. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.
At the time of publication, author Chenshuang Li was affiliated with the Hospital of Stomatology, Peking University. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.