Estrogen modulates bone marrow-derived DCs in SLE murine model-(NZB x NZW) F1 female mice.
Dendritic cells (DCs) in the patient and animal models of systemic lupus erythematosus (SLE) are abnormal, but the detailed mechanism is unclear. Estrogen can modulate DCs in biological condition and estrogen concentration is related to the onset and development of SLE. So the control of estrogen on DCs might lead to the disorder of DCs. To prove the hypothesis, we detected the effects of 17beta-estradiol (E2) on bone marrow (BM)-derived DCs in SLE murine model-(NZB x NZW) F1 (NZB/w F1) female mice before and after the disease onset. We found that E2 mainly enhanced the expression of surface molecule CD40, MHCII and the stimulation activity of immature DCs, but weakened the activity of mature DCs. E2 decreased the production of cytokines IL-6, IL-10, IL-12 and TNFalpha of DCs in young mice, but increased them in old mice. Tamoxifen could antagonize the E2 effect. E2 changed the expression of estrogen receptor-alpha (ER alpha) in DCs. The level of ER alpha in DCs of various old mice and the differentiation states varied. The results suggest that E2 can modulate the functions of BM-derived DCs in SLE pathology. The modulation is achieved by binding ER. The effects of E2 on DCs are different depending on the progression of SLE and cell differentiation status. This might be due to the difference of ER expression.
Jiang
Bo
B
Immunology and Reproductive Biology Lab, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, PR China.
Sun
Lingyun
L
Hao
Sha
S
Li
Xiaoxi
X
Xu
Yixin
Y
Hou
Yayi
Y
D000367:Age Factors; D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004958:Estradiol / Q000276:immunology* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000276:immunology; D004967:Estrogens / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D020845:Selective Estrogen Receptor Modulators / Q000276:immunology / Q000494:pharmacology; D013629:Tamoxifen / Q000276:immunology / Q000494:pharmacology
D019013:CD40 Antigens; D016207:Cytokines; D047628:Estrogen Receptor alpha; D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D004958:Estradiol