Altered interleukin-6 receptor, IL-6R and gp130, production and expression and decreased SOCS-3 expression in placentas from women with pre-eclampsia.
Interleukin-6 (IL-6) and its receptor complex, IL-6 receptor (IL-6R) and gp130, are critical in induction of suppressor of cytokine signalling-3 (SOCS-3) protein, a negative cytokine regulator and anti-inflammatory mediator, in a biological system. Increased inflammatory response is believed to contribute to the placental dysfunction in pre-eclampsia (PE). However, it is not known if altered IL-6 receptor signalling and decreased SOCS-3 expression occur in placentas from PE. To study this, we examined IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130) production by villous tissue from normal and PE placentas. Hypoxia effects on IL-6, sIL-6R and sgp130 production was determined. IL-6R, gp130 and SOCS-3 expression were determined by immunohistochemical staining and by Western blot. Our results showed that under normoxic conditions (21% O(2)), villous tissue from PE placentas produced relative more sgp130, but significantly less IL-6 and sIL-6R (p<0.01) than normal placental tissue. The ratio of sgp130/sIL-6R release was significantly higher by PE placentas than normal placentas, p<0.01. Under hypoxic conditions (2% O(2)), IL-6 production was significantly reduced by both normal (p<0.01) and PE (p<0.05) placental tissue. Hypoxia promoted sgp130 release by normal, but not by PE, placental tissue. Reduced IL-6R and SOCS-3 immunostaining and expression were found in PE placentas. We concluded that increased ratio of sgp130/sIL-6R production and/or reduced sIL-6R production combined with down-regulation of IL-6R and SOCS-3 expression in trophoblasts may lead to less cytokine inhibitory activity in PE placentas, which may account for the increased placental inflammatory response in PE.
Zhao
S
S
Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Gu
Y
Y
Dong
Q
Q
Fan
R
R
Wang
Y
Y
D000328:Adult; D015153:Blotting, Western; D002824:Chorionic Villi / Q000276:immunology / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D010920:Placenta / Q000276:immunology / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D055815:Young Adult
C508600:IL6 protein, human; D015850:Interleukin-6; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D050822:Cytokine Receptor gp130