Interleukin-10 attenuates TNF-alpha-induced interleukin-6 production in endometriotic stromal cells.
OBJECTIVE
To determine whether high levels of interleukin (IL)-10 can attenuate the production of tumor necrosis factor (TNF)-alpha-induced proinflammatory cytokines in endometriotic stromal cells.


METHODS
Prospective study.


METHODS
Department of Ob/Gyn, Tottori University, Japan.


METHODS
Thirty-five patients with ovarian endometrioma and ten patients with uterine myoma.


METHODS
Endometriotic stromal cells were obtained from chocolate cyst linings of ovaries. Endometrial stromal cells obtained from patient with uterine myoma.


METHODS
Expression of IL-10 gene in endometriotic or endometrial stromal cells was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We performed immunohistochemical staining to find the presence of IL-10 and IL-10 receptors 1 and 2. We examined the effects of TNF-alpha and IL-10 on the expression of IL-6 or IL-8 by real-time RT-PCR and ELISA. We examined the activation of intracellular signal transduction molecules in endometriotic stromal cells by Western blotting.


RESULTS
Addition of IL-10 suppressed the expressions of IL-6 induced by TNF-alpha and IL-10 induced the phosphorylation of STAT3 in endometriotic stromal cells. TNF-alpha induced the expression of phosphorylated ERK1/2, JNK1/2, and I kappaB. Adding IL-10 suppressed the phosphorylation of these signal molecules.


CONCLUSIONS
Interleukin-10 attenuates TNF-alpha-induced IL-6 synthesis via NF-kappaB and MAPK pathways in endometriotic cells.. Interleukin-10 may play a significant role in the pathogenesis of endometriosis.
Tagashira
Yukiko
Y
Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.
Taniguchi
Fuminori
F
Harada
Tasuku
T
Ikeda
Ayako
A
Watanabe
Ayako
A
Terakawa
Naoki
N
D017931:DNA Primers; D004715:Endometriosis / Q000188:drug therapy / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007889:Leiomyoma / Q000473:pathology*; D016328:NF-kappa B / Q000235:genetics; D010051:Ovarian Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D053701:Receptors, Interleukin-10 / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*; D014594:Uterine Neoplasms / Q000473:pathology; D000093242:Interleukin-6 Inhibitors
D017931:DNA Primers; D016753:Interleukin-10; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D053701:Receptors, Interleukin-10; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors