Secretion of interleukin-1beta and interleukin-6 by fragments of term human placental villi: signalling pathways and effects of tumour necrosis factor alpha and mode of delivery.
The regulation of cytokine secretion has not been extensively investigated in placental tissue. Fragments of term human placenta were incubated in Tyrode's medium for 3h and cytokine concentrations were measured in the supernatant. IL-1beta secretion after vaginal delivery (VD) was (mean +/- SEM fmol/mg wet weight/3h) 0.193 +/- 0.005 (basal) and 0.549 +/- 0.18 (+1n M TNFalpha) and was more sensitive to TNFalpha dose after elective Caesarean section in the absence of clinical labour (CS) than VD. Secretion of IL-6 after VD was 2.3 +/- 0.47 (basal) and 3.01 +/- 0.34 (+1n M TNFalpha), was correlated with the secretion of IL-1beta and was more sensitive to TNFalpha dose after VD than CS. The inhibitors SB203580, PD98059, SN50, cycloheximide and D-ribofuranosylbenzimidazole each reduced the basal and TNFalpha-stimulated secretion of IL-1beta and also reduced IL-6 secretion with the exception of SN50. There were no interactions between effects of inhibitors and mode of delivery or TNFalpha. In summary we found that term placenta spontaneously secretes IL-1beta and IL-6 in vitro. Delivery after labour alters placental sensitivity to TNFalpha. Exposure to agents known to inhibit MAPK pathways, NF-kappaB, or synthesis of protein and mRNA reduces placental cytokine secretion.
Academic Unit of Child Health, University of Manchester, Research Floor, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK. mark.turner@man.ac.uk
M A
MA
Turner
S A
SA
Shaikh
S L
SL
Greenwood
D000328:Adult; D002585:Cesarean Section; D002824:Chorionic Villi / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D009924:Organ Culture Techniques; D011247:Pregnancy; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D015850:Interleukin-6; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha