Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells
Abstract Background Estrogen signaling is indispensable for muscle regeneration, yet the role of estrogen in the development of muscle inflammation, especially in the intramuscular T cell response, and the influence on the intrinsic immuno-behaviors of myofibers remain largely unknown. We investigat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-07-01
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| Series: | Skeletal Muscle |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13395-019-0205-2 |
| _version_ | 1818506723741138944 |
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| author | Zhao Hong Liao Tao Huang Jiang Wei Xiao Rui Cai Gu Jun Ouyang Gang Wu Hua Liao |
| author_facet | Zhao Hong Liao Tao Huang Jiang Wei Xiao Rui Cai Gu Jun Ouyang Gang Wu Hua Liao |
| author_sort | Zhao Hong Liao |
| collection | DOAJ |
| description | Abstract Background Estrogen signaling is indispensable for muscle regeneration, yet the role of estrogen in the development of muscle inflammation, especially in the intramuscular T cell response, and the influence on the intrinsic immuno-behaviors of myofibers remain largely unknown. We investigated this issue using the mice model of cardiotoxin (CTX)-induced myoinjury, with or without estrogen level adjustment. Methods CTX injection i.m. (tibialis anterior, TA) was performed for preparing mice myoinjury model. Injection s.c. of 17β-estradiol (E2) or estrogen receptor antagonist 4-OHT, or ovariectomy (OVX), was used to change estrogen level of animal models in vivo. Serum E2 level was evaluated by ELISA. Gene levels of estrogen receptor (ERs) and cytokines/chemokines in inflamed muscle were monitored by qPCR. Inflammatory infiltration was observed by immunofluorescence. Macrophage and T cell phenotypes were analyzed by FACS. Immunoblotting was used to assess protein levels of ERs and immunomolecules in C2C12 myotubes treated with E2 or 4-OHT, in the presence of IFN-γ. Results We monitored the increased serum E2 level and the upregulated ERβ in regenerated myofibres after myotrauma. The absence of estrogen in vivo resulted in the more severe muscle inflammatory infiltration, involving the recruitment of monocyte/macrophage and CD4+ T cells, and the heightened proinflammatory (M1) macrophage. Moreover, estrogen signaling loss led to Treg cells infiltration decrease, Th1 response elevation in inflamed muscle, and the markedly expression upregulation of immunomolecules in IFN-γ-stimulated C2C12 myotubes in vitro. Conclusion Our data suggest that estrogen is a positive intervention factor for muscle inflammatory response, through its effects on controlling intramuscular infiltration and phenotypes of monocytes/macrophages, on affecting accumulation and function of Treg cells, and on suppressing Th1 response in inflamed muscle. Our findings also imply an inhibition effect of estrogen on the intrinsic immune behaviors of muscle cells. |
| first_indexed | 2024-12-10T22:08:22Z |
| format | Article |
| id | doaj.art-092caf396b9d4f63bce6973b7d8c4b2e |
| institution | Directory Open Access Journal |
| issn | 2044-5040 |
| language | English |
| last_indexed | 2024-12-10T22:08:22Z |
| publishDate | 2019-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Skeletal Muscle |
| spelling | doaj.art-092caf396b9d4f63bce6973b7d8c4b2e2022-12-22T01:31:40ZengBMCSkeletal Muscle2044-50402019-07-019111610.1186/s13395-019-0205-2Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cellsZhao Hong Liao0Tao Huang1Jiang Wei Xiao2Rui Cai Gu3Jun Ouyang4Gang Wu5Hua Liao6Guangdong Provincial Key Laboratory of Medical Biomechanics, Department of Anatomy, Southern Medical UniversityGuangdong Provincial Key Laboratory of Medical Biomechanics, Department of Anatomy, Southern Medical UniversityGuangdong Provincial Key Laboratory of Medical Biomechanics, Department of Anatomy, Southern Medical UniversityGuangdong Provincial Key Laboratory of Medical Biomechanics, Department of Anatomy, Southern Medical UniversityGuangdong Provincial Key Laboratory of Medical Biomechanics, Department of Anatomy, Southern Medical UniversityDepartment of Emergency, NanFang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Medical Biomechanics, Department of Anatomy, Southern Medical UniversityAbstract Background Estrogen signaling is indispensable for muscle regeneration, yet the role of estrogen in the development of muscle inflammation, especially in the intramuscular T cell response, and the influence on the intrinsic immuno-behaviors of myofibers remain largely unknown. We investigated this issue using the mice model of cardiotoxin (CTX)-induced myoinjury, with or without estrogen level adjustment. Methods CTX injection i.m. (tibialis anterior, TA) was performed for preparing mice myoinjury model. Injection s.c. of 17β-estradiol (E2) or estrogen receptor antagonist 4-OHT, or ovariectomy (OVX), was used to change estrogen level of animal models in vivo. Serum E2 level was evaluated by ELISA. Gene levels of estrogen receptor (ERs) and cytokines/chemokines in inflamed muscle were monitored by qPCR. Inflammatory infiltration was observed by immunofluorescence. Macrophage and T cell phenotypes were analyzed by FACS. Immunoblotting was used to assess protein levels of ERs and immunomolecules in C2C12 myotubes treated with E2 or 4-OHT, in the presence of IFN-γ. Results We monitored the increased serum E2 level and the upregulated ERβ in regenerated myofibres after myotrauma. The absence of estrogen in vivo resulted in the more severe muscle inflammatory infiltration, involving the recruitment of monocyte/macrophage and CD4+ T cells, and the heightened proinflammatory (M1) macrophage. Moreover, estrogen signaling loss led to Treg cells infiltration decrease, Th1 response elevation in inflamed muscle, and the markedly expression upregulation of immunomolecules in IFN-γ-stimulated C2C12 myotubes in vitro. Conclusion Our data suggest that estrogen is a positive intervention factor for muscle inflammatory response, through its effects on controlling intramuscular infiltration and phenotypes of monocytes/macrophages, on affecting accumulation and function of Treg cells, and on suppressing Th1 response in inflamed muscle. Our findings also imply an inhibition effect of estrogen on the intrinsic immune behaviors of muscle cells.http://link.springer.com/article/10.1186/s13395-019-0205-2EstrogenMyoinjuryInflammationEstradiol (E2)C2C12 cell |
| spellingShingle | Zhao Hong Liao Tao Huang Jiang Wei Xiao Rui Cai Gu Jun Ouyang Gang Wu Hua Liao Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells Skeletal Muscle Estrogen Myoinjury Inflammation Estradiol (E2) C2C12 cell |
| title | Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells |
| title_full | Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells |
| title_fullStr | Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells |
| title_full_unstemmed | Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells |
| title_short | Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells |
| title_sort | estrogen signaling effects on muscle specific immune responses through controlling the recruitment and function of macrophages and t cells |
| topic | Estrogen Myoinjury Inflammation Estradiol (E2) C2C12 cell |
| url | http://link.springer.com/article/10.1186/s13395-019-0205-2 |
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