NFkappaB-dependent increase of kynurenine pathway activity in human placenta: Inhibition by sulfasalazine

Poonam Ligam, Ursula Manuelpillai, Euan Wallace, David Walker

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

Catabolism of tryptophan via the kynurenine pathway is up-regulated in the human placenta by infection, resulting in the release of pro-inflammatory and neuroactive metabolites into the fetal circulation. In this study we determined if activation of NFkappaB is involved in the inflammation-induced increase of kynurenine pathway activity in the human placenta. Placentae obtained after elective caesarian section at 37-40 weeks gestation (n=8), and explants (35-40 mg) prepared from terminal villi were incubated under standard conditions in the presence of 10 mug/ml LPS for 24 or 48 h; duplicates of each explant were incubated either with or without 5mM sulfasalazine added to the medium. Expression of mRNAs for key kynurenine-forming enzymes, indoleamine 2,3-dioxygrenase (IDO) and tryptophan 2,3-doalxygenase (TDO) and the inflammatory cytokines TNFalpha and IL6 was studied by RT-PCR. Kynurenine output by explants was measured in samples in the incubation medium by absorbance at 363nm after separation from other metabolites using an HPLC technique. Expression of IDO, TDO, TNFalpha and IL6 mRNAs was increased with LPS treatment, a response mitigated by the presence of sulfasalazine (P
Original languageEnglish
Pages (from-to)997 - 1002
Number of pages6
JournalPlacenta
Volume31
Issue number11
DOIs
Publication statusPublished - 2010

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