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Serotonin-inducible transcription of interleukin-1alpha in uterine smooth muscle cells requires an AP-1 site: cloning and partial characterization of the rat IL-1alpha promoter.

Abstract：

:Interleukin-1 has been shown to contribute to infection-induced inflammatory processes during pregnancy. Prior work from this laboratory has demonstrated that serotonin-induced IL-1alpha also is required for the in-vitro production of collagenase in uterine smooth muscle cells, a normal, non-inflammatory process that occurs in-vivo during post-partum uterine involution. To understand the molecular mechanisms that regulate transcription of the IL-1alpha gene in these cells, we isolated and characterized 1.6 kilobases of the 5'-flanking region of the rat IL-1alpha gene. Sequencing and primer extension identified a single transcription start site and multiple potential regulatory elements, including a TATA box at - 30 bp, a CAAT box at - 74 bp, and a conserved AP-1 site at - 9 bp. This 5'-flanking DNA exhibited low basal promoter activity that was inducible by serotonin. Serotonin-induced promoter activity was unaffected or induced by either medroxyprogesterone or IL-1 receptor antagonist. This occurred despite the ability of both of these hormones to markedly decrease IL-1alpha mRNA. Deletional analysis revealed a strong repressor in the region between - 147 and - 98 bp; removal of this sequence resulted in a fivefold higher basal promoter activity that was still serotonin responsive. Constitutive promoter activity appeared to reside between - 97 and - 22 bp. Deletion of this promoter region, which contained the TATA and CAAT boxes and an NF-IL-6/PEA-3 site, resulted in decreased basal transcriptional activity to the low level seen in larger constructs. Mutational analysis showed that serotonin-inducible transcriptional activity was mediated, at least in part, by the conserved AP-1 site at - 9 bp. This site is located within a larger extended palindromic region: 5'-AAGCCTGACTCAGACTT-3', that together effects both the basal and serotonin-inducible expression of the IL-1alpha gene.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Huang TT,Vinci JM,Lan L,Jeffrey JJ,Wilcox BD

doi

10.1016/s0303-7207(99)00067-2

keywords:

subject

Has Abstract

pub_date

1999-06-25 00:00:00

pages

21-35

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(99)00067-2

journal_volume

152

pub_type

杂志文章

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Serotonin-inducible transcription of interleukin-1alpha in uterine smooth muscle cells requires an AP-1 site: cloning and partial characterization of the rat IL-1alpha promoter.