Interleukin 10 up-regulates elastin gene expression in vivo and in vitro at the transcriptional level.
In immune cells, such as T cells and monocytes, interleukin 10 (IL-10) has regulatory functions on a number of cytokines, including IL-1, IL-2, IL-8 and tumour necrosis factor-alpha expression. However, the effects of IL-10 have not previously been studied in detail in connective-tissue cells. In the present study, we show that recombinant human IL-10 at physiological concentrations has direct effects on the expression of the human elastin gene both in vivo and in vitro. Transgenic mice expressing a human elastin promoter/chloramphenicol acetyltransferase (CAT) reporter gene construct were injected subcutaneously with IL-10 (1-100 ng) and the site of injection was biopsied after 24 h. CAT assay revealed an increase of up to 3.5-fold in the promoter activity with 10 ng of IL-10. Transforming growth factor-beta 2 (TGF-beta 2) is known to up-regulate elastin gene expression in cultured fibroblasts. When IL-10 was added to such cultures, the effects of TGF-beta 2 on elastin mRNA levels were synergistically potentiated. These results suggest that IL-10 has an up-regulatory effect on elastin gene expression.
Reitamo
S
S
Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Remitz
A
A
Tamai
K
K
Ledo
I
I
Uitto
J
J
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004357:Drug Synergism; D004549:Elastin / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation
D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D004549:Elastin