Caspase-1 activation is increased with human labour in foetal membranes and myometrium and mediates infection-induced interleukin-1β secretion.
OBJECTIVE
Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that is involved in human parturition, especially in the context of infection-induced preterm birth. Caspase-1 is a key component of inflammasomes, which are activated upon infection to trigger the maturation of IL-1β.


METHODS
To determine the effect of human labour on caspase-1 activation in human foetal membranes and myometrium. In addition, the mechanisms by which inflammasome activation regulates IL-1β production were also be assessed.


RESULTS
Higher caspase-1 gene and protein expression were detected in foetal membranes myometrium obtained from term labouring women when compared with samples taken from non labouring women. Lipopolysaccharide induced the transcription and secretion of IL-1β from foetal membranes and myometrium; both events were dependent on nuclear factor kappa B (NF-κB). However, levels of extracellular IL-1β were greatly increased by subsequent treatment with the potassium-proton ionophore Adenosine triphosphate (ATP) or nigericin; an effect that was dependent on active caspase-1. Additionally, ATP induced IL-1β secretion via the purinergic P2X7 receptor, whereas the pannexin-1 channel was required for nigericin induced IL-1β secretion.


CONCLUSIONS
Taken together, these results demonstrate that caspase-1 activation is increased with human labour in foetal membranes and myometrium, and is required for infection-induced IL-1β secretion.
Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Vic., Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Vic., Australia.
Martha
M
Lappas
D000255:Adenosine Triphosphate / Q000494:pharmacology; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017630:Connexins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism; D007743:Labor, Obstetric / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009550:Nigericin / Q000494:pharmacology; D011247:Pregnancy; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism
D017630:Connexins; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C492764:PANX1 protein, human; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D020170:Caspase 1; D009550:Nigericin
Caspase-1; IL-1β; foetal membranes; human labour; inflammasome; myometrium