HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by La, E. Articles by Fischer, S. M. Search for Related Content PubMed PubMed Citation Articles by La, E. Articles by Fischer, S. M.

Transcriptional Regulation of Intracellular IL-1 Receptor Antagonist Gene by IL-1 in Primary Mouse Keratinocytes

Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957

The inflammatory cytokine IL-1 mediates inflammatory reactions in skin and up-regulates the expression of other proinflammatory genes. We previously found that IL-1 also increases steady state mRNA levels for intracellular IL-1 receptor antagonist (icIL-1Ra) in primary mouse keratinocytes; however, the mechanism for this was unknown. Here we show that increased expression in primary keratinocytes is due to increased rates of transcription. To study the transcriptional regulation of icIL-1Ra expression induced by IL-1, we functionally characterized 4.5 kb of the 5'-flanking region of the human icIL-1Ra gene. Deletion analysis showed that regulatory elements were contained in the -598- and -288-bp region upstream of the transcription start site. Then we investigated cis- and trans-acting factors required for icIL-1Ra expression and found that a NF-IL-6 site and a NF-B site in the icIL-1Ra promoter were responsible for IL-1-induced icIL-1Ra expression. Moreover, gel shift assays and cotransfection experiments showed that CCAAT/enhancer-binding proteins , , and p65 bind to the NF-IL-6 site and NF-B site, respectively, and functionally trans-activate the icIL-1Ra promoter. Finally, mutational analysis confirmed that these elements were both essential for maximal transcription induced by IL-1.

This article has been cited by other articles:

				T. Wang, S. Bird, A. Koussounadis, J. W. Holland, A. Carrington, J. Zou, and C. J. Secombes Identification of a Novel IL-1 Cytokine Family Member in Teleost Fish J. Immunol., July 15, 2009; 183(2): 962 - 974. [Abstract] [Full Text] [PDF]

				H. Xiong, C. Zhu, F. Li, R. Hegazi, K. He, M. Babyatsky, A. J. Bauer, and S. E. Plevy Inhibition of Interleukin-12 p40 Transcription and NF-{kappa}B Activation by Nitric Oxide in Murine Macrophages and Dendritic Cells J. Biol. Chem., March 12, 2004; 279(11): 10776 - 10783. [Abstract] [Full Text] [PDF]