Lipoxin A4 regulates expression of the estrogen receptor and inhibits 17β-estradiol induced p38 mitogen-activated protein kinase phosphorylation in human endometriotic stromal cells.
OBJECTIVE
To study the role of lipoxin A4 (LXA4) in endometriosis.


METHODS
Molecular analysis in human samples and primary human endometriotic stromal cells (ESCs).


METHODS
University hospital.


METHODS
Forty-nine premenopausal women (30 patients with endometriosis and 19 controls).


METHODS
Normal and ectopic endometrial biopsies obtained during surgery performed during the proliferative phase of the menstrual cycle; ESCs used for in vitro studies.


METHODS
Levels of LXA4 measured by enzyme-linked immunosorbent assay (ELISA); mRNA levels of the estrogen receptor (ER), progestogen receptor (PR), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR); and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation evaluated by Western blotting.


RESULTS
The LXA4 expression level decreased in ectopic tissue as well as ERα and PR, although the expression of ERβ increased in ectopic endometrium compared with the controls. Investigations with correlation analysis revealed the expression of LXA4 was positively correlated with ERα and negatively correlated with ERβ in vivo. Moreover, administering LXA4 could augment ERβ expression in ESCs and inhibit the 17β-estradiol-induced phosphorylation of p38 MAPK very likely through ERβ.


CONCLUSIONS
Our findings indicate that LXA4 regulates ERβ expression and inhibits 17β-estradiol-induced phosphorylation of p38 MAPK, very likely through ERβ in ESCs.
First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Shuo
S
Chen
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, People's Republic of China.
Rong-Feng
RF
Wu
First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Lin
L
Su
First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Wei-Dong
WD
Zhou
First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Mao-Bi
MB
Zhu
First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China. Electronic address: cqhua616@126.com.
Qiong-Hua
QH
Chen
D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D004715:Endometriosis / Q000201:enzymology* / Q000235:genetics; D004717:Endometrium / Q000201:enzymology*; D004789:Enzyme Activation; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D044045:Lipoxins / Q000378:metabolism*; D008875:Middle Aged; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000201:enzymology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C508600:IL6 protein, human; D015850:Interleukin-6; D044045:Lipoxins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D014409:Tumor Necrosis Factor-alpha; C040527:lipoxin A4; D004958:Estradiol; D048051:p38 Mitogen-Activated Protein Kinases
Endometriosis; LXA(4); estrogen receptor; p38 MAPK