Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology
Endometriosis is an estrogen dependent, chronic inflammatory disease characterized by the growth of endometrial lining outside of the uterus. Mast cells have emerged as key players in regulating not only allergic responses but also other mechanisms such as angiogenesis, fibrosis, and pain. The influ...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.961599/full |
| _version_ | 1811344894475632640 |
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| author | Alison McCallion Yasmin Nasirzadeh Harshavardhan Lingegowda Jessica E. Miller Kasra Khalaj SooHyun Ahn Stephany P. Monsanto Mallikarjun Bidarimath Danielle J. Sisnett Andrew W. Craig Steven L. Young Bruce A. Lessey Madhuri Koti Chandrakant Tayade |
| author_facet | Alison McCallion Yasmin Nasirzadeh Harshavardhan Lingegowda Jessica E. Miller Kasra Khalaj SooHyun Ahn Stephany P. Monsanto Mallikarjun Bidarimath Danielle J. Sisnett Andrew W. Craig Steven L. Young Bruce A. Lessey Madhuri Koti Chandrakant Tayade |
| author_sort | Alison McCallion |
| collection | DOAJ |
| description | Endometriosis is an estrogen dependent, chronic inflammatory disease characterized by the growth of endometrial lining outside of the uterus. Mast cells have emerged as key players in regulating not only allergic responses but also other mechanisms such as angiogenesis, fibrosis, and pain. The influence of estrogen on mast cell function has also been recognized as a potential factor driving disease pathophysiology in number of allergic and chronic inflammatory conditions. However, precise information is lacking on the cross talk between endocrine and immune factors within the endometriotic lesions and whether that contributes to the involvement of mast cells with disease pathophysiology. In this study, we observed a significant increase in mast cell numbers within endometriotic lesions compared to matched eutopic endometrium from the same patients. Compared to eutopic endometrium, endometriotic lesions had significantly higher levels of stem cell factor (SCF), a potent growth factor critical for mast cell expansion, differentiation, and survival for tissue resident mast cells. Targeted mRNA Q-PCR array revealed that the endometriotic lesions harbour microenvironment (upregulation of CPA3, VCAM1, CCL2, CMA1, CCR1, and KITLG) that is conducive to mast cells recruitment and subsequent differentiation. To examine cross-talk of mast cells within the endometriotic lesion microenvironment, endometriotic epithelial cells (12Z) and endometrial stromal cells (hESC) incubated with mast cell-conditioned media showed significantly increased production of pro-inflammatory and chemokinetic cytokines. To further understand the impact of estrogen on mast cells in endometriosis, we induced endometriosis in C57BL/6 mice. Mature mast cells were significantly higher in peritoneal fluid of estrogen-treated mice compared to untreated mice within the sham operated groups. Mouse endometriotic lesion tissue revealed several genes (qRT-PCR) relevant in mast cell biology significantly upregulated in the estrogen treated, endometriosis-induced group compared to control endometrium. The endometriotic lesions from estrogen treated mice also had significantly higher density of Alcian blue stained mast cells compared to untreated lesions or control endometrium. Collectively, these findings suggest that endometriotic lesions provide a microenvironment necessary for recruitment and differentiation of mast cells. In turn, mast cells potentially release pro-inflammatory mediators that contribute to chronic pelvic pain and endometriosis disease progression. |
| first_indexed | 2024-04-13T19:54:57Z |
| format | Article |
| id | doaj.art-c66825c49fe44b01b9956b2821788a31 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T19:54:57Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c66825c49fe44b01b9956b2821788a312022-12-22T02:32:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.961599961599Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiologyAlison McCallion0Yasmin Nasirzadeh1Harshavardhan Lingegowda2Jessica E. Miller3Kasra Khalaj4SooHyun Ahn5Stephany P. Monsanto6Mallikarjun Bidarimath7Danielle J. Sisnett8Andrew W. Craig9Steven L. Young10Bruce A. Lessey11Madhuri Koti12Chandrakant Tayade13Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaDepartment of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, CanadaDepartment of Obstetrics and Gynecology, Wake Forest Baptist Health, Winston-Salem, NC, United StatesDepartment of Obstetrics and Gynecology, Wake Forest Baptist Health, Winston-Salem, NC, United StatesDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaEndometriosis is an estrogen dependent, chronic inflammatory disease characterized by the growth of endometrial lining outside of the uterus. Mast cells have emerged as key players in regulating not only allergic responses but also other mechanisms such as angiogenesis, fibrosis, and pain. The influence of estrogen on mast cell function has also been recognized as a potential factor driving disease pathophysiology in number of allergic and chronic inflammatory conditions. However, precise information is lacking on the cross talk between endocrine and immune factors within the endometriotic lesions and whether that contributes to the involvement of mast cells with disease pathophysiology. In this study, we observed a significant increase in mast cell numbers within endometriotic lesions compared to matched eutopic endometrium from the same patients. Compared to eutopic endometrium, endometriotic lesions had significantly higher levels of stem cell factor (SCF), a potent growth factor critical for mast cell expansion, differentiation, and survival for tissue resident mast cells. Targeted mRNA Q-PCR array revealed that the endometriotic lesions harbour microenvironment (upregulation of CPA3, VCAM1, CCL2, CMA1, CCR1, and KITLG) that is conducive to mast cells recruitment and subsequent differentiation. To examine cross-talk of mast cells within the endometriotic lesion microenvironment, endometriotic epithelial cells (12Z) and endometrial stromal cells (hESC) incubated with mast cell-conditioned media showed significantly increased production of pro-inflammatory and chemokinetic cytokines. To further understand the impact of estrogen on mast cells in endometriosis, we induced endometriosis in C57BL/6 mice. Mature mast cells were significantly higher in peritoneal fluid of estrogen-treated mice compared to untreated mice within the sham operated groups. Mouse endometriotic lesion tissue revealed several genes (qRT-PCR) relevant in mast cell biology significantly upregulated in the estrogen treated, endometriosis-induced group compared to control endometrium. The endometriotic lesions from estrogen treated mice also had significantly higher density of Alcian blue stained mast cells compared to untreated lesions or control endometrium. Collectively, these findings suggest that endometriotic lesions provide a microenvironment necessary for recruitment and differentiation of mast cells. In turn, mast cells potentially release pro-inflammatory mediators that contribute to chronic pelvic pain and endometriosis disease progression.https://www.frontiersin.org/articles/10.3389/fimmu.2022.961599/fullendometriosisimmune microenvironmentmast cell recruitment and maturationstem cell factorimmune crosstalkestrogenic inflammation |
| spellingShingle | Alison McCallion Yasmin Nasirzadeh Harshavardhan Lingegowda Jessica E. Miller Kasra Khalaj SooHyun Ahn Stephany P. Monsanto Mallikarjun Bidarimath Danielle J. Sisnett Andrew W. Craig Steven L. Young Bruce A. Lessey Madhuri Koti Chandrakant Tayade Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology Frontiers in Immunology endometriosis immune microenvironment mast cell recruitment and maturation stem cell factor immune crosstalk estrogenic inflammation |
| title | Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology |
| title_full | Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology |
| title_fullStr | Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology |
| title_full_unstemmed | Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology |
| title_short | Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology |
| title_sort | estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology |
| topic | endometriosis immune microenvironment mast cell recruitment and maturation stem cell factor immune crosstalk estrogenic inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.961599/full |
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