PMID- 10499497
OWN - NLM
STAT- MEDLINE
DCOM- 19991012
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 140
IP  - 10
DP  - 1999 Oct
TI  - The expression of interleukin-6 (IL-6), IL-6 receptor, and gp130-kilodalton 
      glycoprotein in the rat decidua and a decidual cell line: regulation by 
      17beta-estradiol and prolactin.
PG  - 4442-50
AB  - The cytokine interleukin 6 (IL-6), a major mediator of immune and acute phase 
      responses of the liver, has been implicated in the termination of pregnancy once 
      expressed in the uterus. This study was undertaken to investigate the expression 
      and regulation of genes encoding IL-6 and IL-6 receptor (IL-6R) in rat decidual 
      tissue. Total RNA obtained from rat decidual tissue on different days of 
      pseudopregnancy was analyzed by RT-PCR using specific primers for IL-6, IL-6R, 
      and 130-kDa glycoprotein (gp130). Ribosomal L19 primers served as an internal 
      control. IL-6R and gp130 were found to be expressed in the decidua throughout 
      development, while no messenger RNA (mRNA) for IL-6 was detected. Interestingly, 
      within several hours of culture, decidual explants acquired the ability to 
      express IL-6. The apparent ability of decidual cells to express IL-6 and its lack 
      of expression in vivo led us to examine whether the IL-6 gene is actively 
      inhibited. Primary decidual cells were cultured in the presence of estradiol, 
      progesterone, or PRL. Progesterone showed no effect, whereas estradiol and PRL 
      reduced the level of IL-6 mRNA expression. To examine the mechanism by which 
      these hormones inhibit IL-6 expression, we used a simian virus 40-transformed 
      decidual cell line (GG-AD), which expresses only estrogen receptor-beta (ERbeta). 
      Like primary decidual cells in culture, GG-AD cells express IL-6, IL-6R, and 
      gp130 mRNA. When cultured in the presence of estradiol (0-100 ng/ml), mRNA for 
      IL-6 and its receptor components were down-regulated in a dose-dependent manner. 
      Estradiol also caused a dose-dependent decrease in IL-6 protein secretion into 
      the culture medium. The inhibitory effect of estradiol on IL-6 mRNA expression 
      was reversed by the antiestrogen ICI-164,384. Similar inhibition of IL-6 and 
      gp130 mRNA expression was observed with PRL treatment. However, PRL had no effect 
      on IL-6R mRNA levels. PRL inhibition of IL-6 expression was totally reversed by 
      tyrphostin AG490, a JAK2 inhibitor. In summary, the results of this investigation 
      indicate that IL-6 expression, which is detrimental to the maintenance of 
      pregnancy, is inhibited in the rat decidual tissue. This inhibition is induced by 
      PRL and estradiol, which down-regulate not only IL-6 expression, but also the 
      expression of IL-6 receptor and signaling proteins. The results also suggest that 
      PRL signaling to the IL-6 gene is mediated through the long form of PRL receptor 
      and involves JAK2 activation, whereas that of estradiol can be transduced by 
      estrogen receptor-beta.
FAU - Deb, S
AU  - Deb S
AD  - Department of Physiology and Biophysics, University of Illinois College of 
      Medicine, Chicago 60612-7342, USA.
FAU - Tessier, C
AU  - Tessier C
FAU - Prigent-Tessier, A
AU  - Prigent-Tessier A
FAU - Barkai, U
AU  - Barkai U
FAU - Ferguson-Gottschall, S
AU  - Ferguson-Gottschall S
FAU - Srivastava, R K
AU  - Srivastava RK
FAU - Faliszek, J
AU  - Faliszek J
FAU - Gibori, G
AU  - Gibori G
LA  - eng
GR  - HD-11119/HD/NICHD NIH HHS/United States
GR  - HD-12356/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Antigens, CD)
RN  - 0 (Il6st protein, rat)
RN  - 0 (Interleukin-6)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin-6)
RN  - 133483-10-0 (Cytokine Receptor gp130)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 4TI98Z838E (Estradiol)
RN  - 9002-62-4 (Prolactin)
SB  - IM
MH  - Animals
MH  - Antigens, CD/*metabolism
MH  - Cell Line
MH  - Culture Techniques
MH  - Cytokine Receptor gp130
MH  - Decidua/cytology/drug effects/*metabolism
MH  - Estradiol/pharmacology/physiology
MH  - Female
MH  - Interleukin-6/genetics/*metabolism
MH  - Membrane Glycoproteins/*metabolism
MH  - Progesterone/pharmacology
MH  - Prolactin/pharmacology/physiology
MH  - Pseudopregnancy/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Interleukin-6/*metabolism
EDAT- 1999/09/28 00:00
MHDA- 1999/09/28 00:01
CRDT- 1999/09/28 00:00
PHST- 1999/09/28 00:00 [pubmed]
PHST- 1999/09/28 00:01 [medline]
PHST- 1999/09/28 00:00 [entrez]
AID - 10.1210/endo.140.10.7063 [doi]
PST - ppublish
SO  - Endocrinology. 1999 Oct;140(10):4442-50. doi: 10.1210/endo.140.10.7063.