REGULATION OF INTERLEUKIN-4 ON COLLAGEN GENE-EXPRESSION BY SYSTEMIC-SCLEROSIS FIBROBLASTS IN CULTURE

This study was performed to evaluate the transcriptional regulation of interleukin-4 (IL-4) on collagen gene expression in systemic sclerosi s (SSc) fibroblasts. The pro alpha 2(I) collagen promotor activity has been examined by transfection experiments and chloramphenicol acetyl transferase (CAT) assay. Maximal elevation of collagen synthesis was p resented at a concentration of 5 ng/ml of IL-4. In the CAT assay, the percentage of acetylation was 7.0% +/- 2.0% in untreated controls and 12.5% +/- 3.5% in SSc fibroblasts at 5.0 ng/ml of IL-4. In normal skin (NS), 3.5% +/- 1.0%, and 10.2% +/- 2.5% were acetylated, respectively . The promoter activity was increased 1.8 +/- 0.7-fold and 2.9 +/- 1.3 -fold in IL-4-treated SSc and NS, respectively, as compared to untreat ed groups. In Northern and dot-blot analysis, the level, of types I an d III collagen mRNA increased 1.1 +/- 0.3-fold and 1.3 +/- 0.3-fold, r espectively, in IL-4-treated SSc fibroblasts compared to 3.0 +/- 0.4-f old and 3.0 +/- 0.3-fold, respectively, in NS fibroblasts. These data may indicate that IL-4 could be important in promoting biogenesis of c ollagen proteins by increased stability and transcription of the colla gen mRNA. Also, transcriptional activation of collagen gene expression appears to have a less sensitive effect on SSc than on NS.