Submitted August 23, 2007
Returned for revision September 13, 2007
Accepted March 3, 2008
Female Reproductive Tract
Interleukin 1 Signaling Is Regulated by Leukemia Inhibitory Factor (LIF) and Is Aberrant in Lif -/- Mouse Uterus
A. A. Fouladi-Nashta ,
L. Mohamet ,
J. K. Heath ,
and
S. J. Kimber *
* To whom correspondence should be addressed. E-mail: sue.kimber{at}manchester.ac.uk.
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 (D) 4 am with renewed expression by D4 pm. In Lif -/- LE there was a gradual decrease in expression from D2 which 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 am reappearing on D4 pm, but in the null mice was only expressed on D3 and D5. Stromal Il1r1 and Il1r2 were also misregulated. Il1rn showed constitutive expression in null stroma in contrast to the loss of expression on D4 am 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 co-culture revealed that LIF stimulated 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.
Key words:
Implantation •
Uterus •
Leukemia Inhibitory Factor •
interleukin-1 •
prostaglandin
