Leukoregulin, a T cell-derived cytokine, induces IL-8 gene expression and secretion in human skin fibroblasts. Demonstration and secretion in human skin fibroblasts. Demonstration of enhanced NF-kappa B binding and NF-kappa B-driven promoter activity - PubMed (original) (raw)

. 1992 Nov 1;149(9):2969-76.

Affiliations

PMID: 1401924

Leukoregulin, a T cell-derived cytokine, induces IL-8 gene expression and secretion in human skin fibroblasts. Demonstration and secretion in human skin fibroblasts. Demonstration of enhanced NF-kappa B binding and NF-kappa B-driven promoter activity

A Mauviel et al. J Immunol. 1992.

Abstract

It was shown previously that leukoregulin (LR), a T cell-derived cytokine with unique antitumor properties, modulates fibroblast functions in vitro, including prostaglandin production, matrix synthesis, and protease gene expression. Here, we have focused on the ability of LR to modulate IL-8 gene expression in human dermal fibroblasts. Using a specific ELISA, we demonstrated a dose-dependent enhancement of IL-8 production by LR, accompanied by a parallel elevation of the corresponding mRNA levels, as measured by Northern hybridizations. Maximum accumulation of IL-8 mRNA was observed after 6 h of incubation with LR, and the elevation persisted over 24 h. Inhibition of protein synthesis by cycloheximide resulted in superinduction of IL-8 mRNAs by LR. Dexamethasone, all-trans-retinoic acid, and TGF-beta 1 failed to counteract the effect of LR on IL-8 gene expression. Transient cell transfections with an IL-8 promoter/CAT reporter gene construct showed a dose-dependent enhancement of the promoter activity by LR, suggesting transcriptional regulation. Gel shift assays with oligonucleotides containing the consensus NF-kappa B binding sequences of the IL-8 and Ig kappa light chain genes showed enhanced binding activity in nuclear extracts from cells incubated with LR. Transient transfection experiments using a NF-kappa B/SV2 promoter-CAT reporter gene construct showed enhanced CAT activity by LR. Taken together, these data suggest that LR may up-regulate IL-8 gene expression by activation of the binding of NF-kappa B to the corresponding cis-acting element in the IL-8 promoter. Our results demonstrate that LR, together with IL-1 and TNF-alpha, could participate in the recruitment of neutrophils to the sites of inflammation by induction of IL-8 production in fibroblasts.

PubMed Disclaimer

Cited by

Calcitonin gene-related peptide inhibits chemokine production by human dermal microvascular endothelial cells.
Huang J, Stohl LL, Zhou X, Ding W, Granstein RD. Huang J, et al. Brain Behav Immun. 2011 May;25(4):787-99. doi: 10.1016/j.bbi.2011.02.007. Epub 2011 Feb 18. Brain Behav Immun. 2011. PMID: 21334428 Free PMC article.
RelB regulation of chemokine expression modulates local inflammation.
Xia Y, Pauza ME, Feng L, Lo D. Xia Y, et al. Am J Pathol. 1997 Aug;151(2):375-87. Am J Pathol. 1997. PMID: 9250151 Free PMC article.
Fibroblasts as sentinel cells. Synthesis of chemokines and regulation of inflammation.
Smith RS, Smith TJ, Blieden TM, Phipps RP. Smith RS, et al. Am J Pathol. 1997 Aug;151(2):317-22. Am J Pathol. 1997. PMID: 9250144 Free PMC article. Review.

Leukoregulin, a T cell-derived cytokine, induces IL-8 gene expression and secretion in human skin fibroblasts. Demonstration and secretion in human skin fibroblasts. Demonstration of enhanced NF-kappa B binding and NF-kappa B-driven promoter activity - PubMed (original) (raw)