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This Article Full Text Full Text (PDF) All Versions of this Article: 79/1/142    most recent biolreprod.107.065219v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Fouladi-Nashta, A.A Articles by Kimber, S.J PubMed PubMed Citation Articles by Fouladi-Nashta, A.A Articles by Kimber, S.J Agricola Articles by Fouladi-Nashta, A.A Articles by Kimber, S.J

Interleukin 1 Signaling Is Regulated by Leukemia Inhibitory Factor (LIF) and Is Aberrant in Lif^–/– Mouse Uterus¹

Faculty of Life Sciences,⁵ The University of Manchester, Core Technology Facility, Manchester M13 9MNT, United Kingdom School of Biosciences,⁶ University of Birmingham, Birmingham B15 2TT, United Kingdom

ABSTRACT

This study addresses the regulation of the interleukin 1 (IL1) system in the murine uterine luminal epithelium (LE) and stroma by leukemia inhibitory factor (LIF). Using RT-PCR we compared expression of Il1a, Il1b, Il1rn, Il1r1, and Il1r2 during the pre- and peri-implantation periods of pregnancy in wild-type (WT) and LIF-null LE and stroma. In WT LE, Il1a transcripts were down-regulated on Day 4 of pregnancy (D4), with renewed expression by the evening of D4 (D4 pm). In Lif ^–/– LE there was a gradual decrease in expression on D2, and expression became undetectable by D6. Il1b and Il1r1 expression were similar in WT and null mice, but Il1rn expression was almost completely lost during the peri-implantation period in Lif ^–/– LE. In the stroma, Il1a was sharply down-regulated on D4 and reappeared on D4 pm but was only expressed from D3 to D5 in the null mice. Stromal Il1r1 and Il1r2 were also misregulated. Il1rn showed constitutive expression in null stroma in contrast to the loss of expression on D4 in the WT mouse. In Lif-deficient mice, immunostaining indicated a reduction of endometrial IL1A at the time of implantation and of IL1B in stroma. LE-stromal coculture revealed that LIF stimulated the apical secretion of both IL1A and PTGES2 by LE cells without affecting basal secretion of IL1A and with only a small effect on basal PTGES2 secretion. We conclude that Il1a and Il1rn in LE and Il1a, Il1rn, and Il1r1 in stroma are regulated by LIF, which stimulates apical secretion of IL1A by LE.

implantation, interleukin 1, leukemia inhibitory factor, prostaglandin, uterus

⁴These authors contributed equally to this work.

³Current address: The Royal Veterinary College, Hawkshead Lane, Hatfield AL9 7TA, United Kingdom.

¹Supported by a grant from the Biological and Biotechnological Research Council (BBSRC) United Kingdom to S.J.K. and a BBSRC graduate studentship to L.M.

Correspondence: ²FAX: 161 275 3915; e-mail: sue.kimber{at}manchester.ac.uk