PMID- 9141553
OWN - NLM
STAT- MEDLINE
DCOM- 19970523
LR  - 20151119
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 82
IP  - 5
DP  - 1997 May
TI  - Hypoxia stimulates cytokine production by villous explants from the human 
      placenta.
PG  - 1582-8
AB  - It has been hypothesized that inadequate placentation in the hypertensive 
      disorder of pregnancy known as preeclampsia creates foci of placental 
      ischemia/hypoxia leading to the elaboration of factors that compromise systemic 
      endothelial function to produce disease sequelae. As tumor necrosis factor-alpha 
      (TNF alpha) and interleukin-1 (IL-1) are inflammatory cytokines capable of 
      eliciting endothelial cell dysfunction, we investigated whether the production of 
      these inflammatory cytokines by cultured villous explants from the human placenta 
      was affected by incubation in reduced oxygen (2% O2). The term placenta produced 
      TNF alpha, IL-6, and low levels of IL-1alpha and IL-1beta under standard tissue 
      culture conditions. Hypoxia significantly increased TNF alpha, IL-1alpha, and 
      IL-1beta production by 2-, 6-, and 23-fold, respectively, but did not affect IL-6 
      production. Further, cytokines were immunolocalized to the syncytiotrophoblast 
      layer as well as to some villous core cells. Hypoxic regulation of placental TNF 
      alpha and IL-1beta production also appeared to differ based on gestational age. 
      Finally, treatment with either cobalt chloride or an iron chelator mimicked the 
      hypoxic response, suggesting that stimulation of placental cytokine production 
      may involve a heme-containing, O2-sensing protein. These results suggest that 
      placental hypoxia can lead to the elaboration of inflammatory cytokines, which 
      may contribute to the pathophysiology of preeclampsia.
FAU - Benyo, D F
AU  - Benyo DF
AD  - Magee-Womens Research Institute and the Department of Obstetrics, Gynecology, and 
      Reproductive Sciences, University of Pittsburgh School of Medicine, Pennsylvania 
      15213, USA.
FAU - Miles, T M
AU  - Miles TM
FAU - Conrad, K P
AU  - Conrad KP
LA  - eng
GR  - KO4-HD-01098/HD/NICHD NIH HHS/United States
GR  - P01 HD30367/HD/NICHD NIH HHS/United States
GR  - R01-HD-30325/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3G0H8C9362 (Cobalt)
RN  - 4X87R5T106 (1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt)
RN  - EVS87XF13W (cobaltous chloride)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt/pharmacology
MH  - Cobalt/pharmacology
MH  - Culture Techniques
MH  - Cytokines/*biosynthesis
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunosorbent Techniques
MH  - Interleukin-1/analysis/biosynthesis
MH  - Interleukin-6/analysis/biosynthesis
MH  - Oxygen/*administration & dosage
MH  - Placenta/chemistry/drug effects/*metabolism
MH  - Pregnancy
MH  - Trophoblasts/chemistry
MH  - Tumor Necrosis Factor-alpha/analysis/biosynthesis
EDAT- 1997/05/01 00:00
MHDA- 1997/05/01 00:01
CRDT- 1997/05/01 00:00
PHST- 1997/05/01 00:00 [pubmed]
PHST- 1997/05/01 00:01 [medline]
PHST- 1997/05/01 00:00 [entrez]
AID - 10.1210/jcem.82.5.3916 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1997 May;82(5):1582-8. doi: 10.1210/jcem.82.5.3916.