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Involving the Nuclear Transcription Factor
NF
B
Abstract
Endometriosis, the ectopic development of endometrial
tissue, is, at least peritoneal endometriosis, believed to
result from tubal reflux of menstrual tissue. The release
of cytokines and growth factors by refluxed endometrial
cells in response to peritoneal inflammatory stimuli may
enhance the capability of endometrial cells to implant and
grow into the peritoneal host tissue. Herein we report
that interleukin 1 (IL1), a major pro-inflammatory
cytokine which is overproduced by endometriosis
women-derived peritoneal macrophages and found in elevated
concentrations in the peritoneal fluid of endometriosis
patients, stimulates the synthesis and the secretion of
macrophage migration inhibitory factor (MIF) by human
endometrial stromal cells. IL1B (0.1-100 ng/ml) exerted a
dose- and time-dependent effects of MIF protein
secretion and mRNA synthesis, as shown by enzyme-linked
immunosorbent assay (ELISA) and reverse
transcription-polymerase chain reaction (RT-PCR),
respectively. IL1B appeared to induce MIF gene
transcription via the nuclear transcription factor
NF
B, as shown by electrophoretic mobility shift
assay (EMSA) and Western blot analysis of I
B
phosphorylation. Curcumin (10-8 M), which is
known for inhibiting NF
B activation, inhibited
IL1B-induced MIF secretion as well as NF
B nuclear
translocation and DNA binding. Taken together these
findings clearly show that IL1B up-regulates the
expression of MIF in endometrial stromal cells in
vitro and acts via NF
B. This may play an
important role in the physiology of the human endometrium
and the pathophysiology of endometriosis considering the
immunomodulatory properties of MIF as well as its role in
cell growth, angiogenesis and tissue remodeling.
Key words:
Female Reproductive Tract
Cytokines
Menstrual cycle
Uterus
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