MOLECULAR ANALYSIS OF CONSTITUTIVE IL-1α GENE EXPRESSION IN HUMAN MELANOMA CELLS: AUTHOCRINE STIMULATION THROUGH NF-κB ACTIVATION BY ENDOGENOUS IL-1α

doi:10.1006/cyto.1998.0369

Cytokine

Volume 10, Issue 11, November 1998, Pages 872-879

https://doi.org/10.1006/cyto.1998.0369 Get rights and content

Abstract

Constitutive production of/and acquired resistance to anti-proliferative cytokines are implicated in pathogenesis and progression of human melanoma cells. Human melanoma cells A375-C6 are sensitive to interleukin 1 (IL-1) anti-proliferative effect and do not produce IL-1. After long period of culture we have obtained cells which acquired resistance to IL-1. The resistant cells exhibited constitutive production of IL-1α. To analyse the mechanisms that lead to the expression of IL-1α in the cells, we transfected of the resistant clone A375-R8 with CAT (chloramphenicol acetyltransferase) expression plasmids linked to a 5'-flanking deletion mutants of the human IL-1α gene. Two nucleotide regions (−103 to −70 bp) and (−70 to −47 bp) from the start of the first exon appeared to contain a positive regulatory element(s), while the one −310 to −092 bp contained a negative regulatory element(s). The −103 to −70 bp region contained the consensus NF-κB (nuclear factor-κB) binding motif. Immunofluorescence analysis revealed that NF-κB is activated in A375-R8 cells. IL-1 receptor antagonist (IL-1Ra) decreased the level of IL-1α mRNA and production of IL-1α. IL-1Ra also inhibited the localization of p65 in the nuclei and CAT activity in transfectants with the plasmids containing NF-κB binding motif. These results indicate that endogenous IL-1α stimulates the gene expression and production of IL-1α in an autocrine manner through activation of NF-κB.

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Citation Excerpt :
The second stage of inflammation is mediated mainly by macrophages, which phagocytose the target cells and secrete other, primarily immunosuppressive cytokines, such as certain interleukins, including IL-10, and TGF-β. The general characteristics of the principal cytokines implicated in glaucoma are presented in Table 1 [10,30–47]. For increased clarity, due to the variety of studies, we have chosen to present the expression of cytokines on one hand in the AH and on the other hand in the healthy, then glaucomatous, trabecular meshwork.
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^☆: Correspondence to: Marcel van Deuren, Department of General Internal Medicine, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands

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Regular articleMOLECULAR ANALYSIS OF CONSTITUTIVE IL-1α GENE EXPRESSION IN HUMAN MELANOMA CELLS: AUTHOCRINE STIMULATION THROUGH NF-κB ACTIVATION BY ENDOGENOUS IL-1α☆

Abstract

Regular article
MOLECULAR ANALYSIS OF CONSTITUTIVE IL-1α GENE EXPRESSION IN HUMAN MELANOMA CELLS: AUTHOCRINE STIMULATION THROUGH NF-κB ACTIVATION BY ENDOGENOUS IL-1α☆