Interleukin-6- and tumour necrosis factor alpha-mediated expression of hepatocyte growth factor by stromal cells and its involvement in the growth of endometriosis.
BACKGROUND
We investigated the expression of the hepatocyte growth factor (HGF) gene and protein by the stromal cells derived from women with or without endometriosis and its regulation by interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFalpha).


METHODS
Stromal cells immunoreactive to vimentin were isolated from the eutopic and ectopic endometrium of 18 infertile women with endometriosis and 12 women without endometriosis. The production of HGF in the culture media of basal and IL-6- or TNFalpha-stimulated stromal cells was examined with an enzyme-linked immunosorbent assay. The mRNA expression of HGF and its receptor c-Met in the stroma was investigated by RT-PCR. The localization of HGF and c-Met in isolated stromal cells and in intact tissue was examined by immunohistochemistry. The effect of HGF on the growth of stromal cells alone or in combination with IL-6 or TNFalpha was examined in a bromodeoxyuridine (BrdU) incorporation study.


RESULTS
The production of HGF in the culture medium of stromal cells was significantly increased after single or combined treatment with either IL-6 or TNFalpha when compared with non-treated cells. The production of HGF by stromal cells derived from the eutopic endometrium of women with endometriosis was significantly higher than that of cells from women without endometriosis. This effect was paralleled by increased expression of HGF and c-Met mRNA, as demonstrated by RT-PCR. The BrdU incorporation study indicated that the addition of HGF enhanced the growth of endometrial and endometriotic stroma alone or in combination with IL-6 or TNFalpha.


CONCLUSIONS
IL-6 and TNFalpha are involved in the production of HGF by endometrial stromal cells and may be involved in the growth of endometriosis by an autocrine mechanism.
Khan
Khaleque Newaz
KN
Department of Obstetrics and Gynecology, Nagasaki University, Japan. nemokhan@net.nagasaki-u.ac.jp
Masuzaki
Hideaki
H
Fujishita
Akira
A
Kitajima
Michio
M
Hiraki
Koichi
K
Sekine
Ichiro
I
Matsuyama
Toshifumi
T
Ishimaru
Tadayuki
T
D000963:Antimetabolites / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation; D003470:Culture Media; D018450:Disease Progression; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D000963:Antimetabolites; D003470:Culture Media; D007074:Immunoglobulin G; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014746:Vimentin; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D001973:Bromodeoxyuridine