Article ; Online: Glucocorticoids and medroxyprogesterone acetate synergize with inflammatory stimuli to selectively upregulate CCL20 transcription.
Molecular and cellular endocrinology
2023 Volume 563, Page(s) 111855
Abstract: The pro-inflammatory cytokine, chemokine (C-C motif) ligand 20 (CCL20), is emerging as a therapeutic target for immune-based therapies. Cooperative regulation of CCL20 by glucocorticoids and progestins used in endocrine therapy and pro-inflammatory ... ...
| Abstract | The pro-inflammatory cytokine, chemokine (C-C motif) ligand 20 (CCL20), is emerging as a therapeutic target for immune-based therapies. Cooperative regulation of CCL20 by glucocorticoids and progestins used in endocrine therapy and pro-inflammatory mediators could modulate immune function and affect disease outcomes. We show that glucocorticoids as well as medroxyprogesterone acetate (MPA), the progestin widely used in injectable contraception in sub-Saharan Africa, cooperate with pro-inflammatory mediators to upregulate CCL20 protein and/or mRNA in human peripheral blood mononuclear cells (PBMCs) and human cervical cell lines. Changes in CCL20 mRNA levels were shown to be synergistic, as assessed by Chou analysis, cell- and gene-specific and to involve transcriptional regulation, with a requirement for a nuclear factor kappa B (NF-κB) site and glucocorticoid receptor (GR) involvement. The novel results suggest a mechanism whereby MPA, like glucocorticoids, may impact inflammation both systemically and in the genital tract in patients using MPA and/or glucocorticoid therapy. |
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| MeSH term(s) | Humans ; Medroxyprogesterone Acetate/pharmacology ; Glucocorticoids/pharmacology ; Glucocorticoids/metabolism ; Leukocytes, Mononuclear/metabolism ; Progestins/metabolism ; Receptors, Glucocorticoid/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Chemokine CCL20/genetics ; Chemokine CCL20/metabolism |
| Chemical Substances | Medroxyprogesterone Acetate (C2QI4IOI2G) ; Glucocorticoids ; Progestins ; Receptors, Glucocorticoid ; RNA, Messenger ; CCL20 protein, human ; Chemokine CCL20 |
| Language | English |
| Publishing date | 2023-01-13 |
| Publishing country | Ireland |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. |
| ZDB-ID | 187438-x |
| ISSN | 1872-8057 ; 0303-7207 |
| ISSN (online) | 1872-8057 |
| ISSN | 0303-7207 |
| DOI | 10.1016/j.mce.2023.111855 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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