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Analysis of interleukin-1beta-modulated mRNA gene transcription in human gingival keratinocytes by epithelia-specific cDNA microarrays.

Abstract：

BACKGROUND/OBJECTIVES:Proinflammatory cytokines such as interleukin-1beta are known to be synthesized in oral gingivitis and periodontitis and lead to the activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Although numerous effects of interleukin-1beta on mesenchymal cells are known, e.g. up-regulation of intercellular adhesion molecule-1 in endothelial cells, little is known of the effects of interleukin-1beta on oral keratinocytes. The purpose of the present study was to seek interleukin-1beta-mediated alterations in mRNA gene transcription and a putative activation of NF-kappaB in oral gingival keratinocytes. METHODS:As an in vitro model for gingivitis and periodontitis, immortalized human gingival keratinocytes (IHGK) were stimulated with the proinflammatory cytokine interleukin-1beta. An epithelia-specific cDNA microarray was used to analyze mRNA expression profiles from IHGK cells treated with 200 units interleukin-1beta/ml for 3, 6, 9, 12, and 24 h. Indirect immunofluorescence was carried out to detect NF-kappaB in IHGK following interleukin-1beta treatment. RESULTS:Detailed analysis revealed distinct patterns of time-dependent changes, including genes induced or repressed early (3-6 h) or late (12-24 h) after interleukin-1beta treatment. Differentially expressed genes were involved in (i) cell stress, (ii) DNA repair, (iii) cell cycle and proliferation, (iv) anti-pathogen response, (v) extracellular matrix turnover, and (vi) angiogenesis. A large number of genes were responsive to NF-kappaB and induction was concomitant with nuclear translocation of the p65 RelA subunit of NF-kappaB. Interestingly, many of these genes contain multiple NF-kappaB binding sites in their promoters. CONCLUSION:Analysis of altered gene expression allows identification of gene networks associated with inflammatory responses. In addition to a number of well-known genes involved in gingivitis and periodontitis, we identified novel candidates that might be associated with the onset and maintenance of an inflammatory disease.

journal_name

J Periodontal Res

journal_title

Journal of periodontal research

authors

Steinberg T,Dannewitz B,Tomakidi P,Hoheisel JD,Müssig E,Kohl A,Nees M

doi

10.1111/j.1600-0765.2006.00884.x

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

426-46

issue

eissn

0022-3484

issn

1600-0765

pii

JRE884

journal_volume

pub_type

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Analysis of interleukin-1beta-modulated mRNA gene transcription in human gingival keratinocytes by epithelia-specific cDNA microarrays.