Τίτλος:
Estrogen anti-inflammatory activity on human monocytes is mediated through cross-talk between estrogen receptor ERα36 and GPR30/GPER1
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Estrogens are known modulators of monocyte/macrophage functions; however, the underlying mechanism has not been clearly defined. Recently, a number of estrogen receptor molecules and splice variants were identified that exert different and sometimes opposing actions. We assessed the expression of estrogen receptors and explored their role in mediating estrogenic anti-inflammatory effects on human primary monocytes. We report that the only estrogen receptors expressed are estrogen receptor-α 36-kDa splice variant and G-protein coupled receptor 30/G-protein estrogen receptor 1, in a sex-independent manner. 17-β-Estradiol inhibits the LPS-induced IL-6 inflammatory response, resulting in inhibition of NF-κB transcriptional activity. This is achieved via a direct physical interaction of ligand-activated estrogen receptor-α 36-kDa splice variant with the p65 component of NF-κB in the nucleus. G-protein coupled receptor 30/G-protein estrogen receptor 1, which also physically interacts with estrogen receptor-α 36-kDa splice variant, acts a coregulator in this process, because its inhibition blocks the effect of estrogens on IL-6 expression. However, its activation does not mimic the effect of estrogens, on neither IL-6 nor NF-κB activity. Finally, we show that the estrogen receptor profile observed in monocytes is not modified during their differentiation to macrophages or dendritic cells in vitro and is shared in vivo by macrophages present in atherosclerotic plaques. These results position estrogen receptor-α 36-kDa splice variant and G-protein coupled receptor 30 as important players and potential therapeutic targets in monocyte/macrophage-dependent inflammatory processes. © Society for Leukocyte Biology.
Συγγραφείς:
Pelekanou, V.
Kampa, M.
Kiagiadaki, F.
Deli, A.
Theodoropoulos, P.
Agrogiannis, G.
Patsouris, E.
Tsapis, A.
Castanas, E.
Notas, G.
Περιοδικό:
Journal of Leukocyte Biology
Εκδότης:
Federation of American Societies for Experimental Biology
Λέξεις-κλειδιά:
estradiol; estrogen receptor alpha; estrogen receptor alpha 36; G protein coupled receptor; G protein coupled receptor 30; G protein estrogen receptor 1; interleukin 6; transcription factor RelA; unclassified drug; antiinflammatory agent; estradiol; estrogen receptor; estrogen receptor alpha; estrogen receptor alpha, human; fulvestrant; G protein coupled receptor; GPER protein, human; IL6 protein, human; interleukin 6; isoprotein; lipopolysaccharide; RELA protein, human; small interfering RNA; transcription factor RelA, antiinflammatory activity; Article; atherosclerotic plaque; cell activation; cell differentiation; cell nucleus; clinical article; controlled study; coronary artery atherosclerosis; cytokine production; dendritic cell; drug mechanism; estrogen activity; female; foam cell; hormone receptor interaction; human; human cell; human tissue; in vitro study; in vivo study; macrophage; male; molecular weight; monocyte; priority journal; splicing defect; aged; analogs and derivatives; biosynthesis; chemistry; coronary artery disease; drug effects; genetic transcription; genetics; inflammation; metabolism; middle aged; monocyte; myelopoiesis; pathology; physiology; protein analysis; reporter gene; RNA interference; signal transduction; tumor cell line, Aged; Anti-Inflammatory Agents; Cell Line, Tumor; Cell Nucleus; Coronary Artery Disease; Dendritic Cells; Estradiol; Estrogen Receptor alpha; Female; Foam Cells; Genes, Reporter; Humans; Inflammation; Interleukin-6; Lipopolysaccharides; Macrophages; Male; Middle Aged; Monocytes; Myelopoiesis; Protein Interaction Mapping; Protein Isoforms; Receptor Cross-Talk; Receptors, Estrogen; Receptors, G-Protein-Coupled; RNA Interference; RNA, Small Interfering; Transcription Factor RelA; Transcription, Genetic
DOI:
10.1189/jlb.3A0914-430RR
