Gene interactions and pathways from curated databases and text-mining
Clin Cancer Res 2001, PMID: 11410524

IL (interleukin)-1alpha promotes nuclear factor-kappaB and AP-1-induced IL-8 expression, cell survival, and proliferation in head and neck squamous cell carcinomas.

Wolf, J S; Chen, Z; Dong, G; Sunwoo, J B; Bancroft, C C; Capo, D E; Yeh, N T; Mukaida, N; Van Waes, C

Interleukin 1alpha (IL-1alpha) is an important regulatory cytokine, the release of which after an injury can induce activation of transcription factors nuclear factor (NF)kappaB and activator protein (AP-1), which promote expression of genes involved in cell survival, proliferation, and angiogenesis. IL-1alpha is expressed autonomously by head and neck squamous cell carcinomas (HNSCCs) and a variety of other cancers, raising the possibility that IL-1alpha may serve as an autocrine factor that stimulates the activation of prosurvival transcription factors and target genes in cancer. In this study, we examined the role of IL-1alpha in the activation of NFkappaB and AP-1, the expression of proangiogenic cytokine IL-8, and in the survival and proliferation of HNSCC cell lines. HNSCCs were found to secrete and respond to functional IL-1alpha, in that culture supernatant from a high IL-1alpha-secreting line, UM-SCC-11B, could induce secretion of cytokine IL-8 by a low IL-1alpha-secreting line, UM-SCC-9; and the induction of IL-8 secretion could be blocked by the anti-IL-1alpha-neutralizing antibody or the IL-1 receptor antagonist (IL-1RA). Furthermore, IL-1alpha could induce the expression of IL-8 through an autocrine mechanism, in that transfection of UM-SCC-9 cells with a plasmid encoding IL-1alpha resulted in the increased coexpression of IL-1alpha and IL-8; whereas transfection with a plasmid encoding IL-1RA lacking the secretory leader sequence led to the decreased coexpression of IL-1alpha and IL-8. IL-1alpha was found to induce coexpression of IL-8 through the activation of NFkappaB and AP-1, in that mutation of the NFkappaB site within the IL-8 promoter abolished autocrine- and recombinant IL-1alpha-induced IL-8 reporter gene activity, whereas mutation in AP-1 partially decreased IL-8 reporter gene activity in UM-SCC-9 cells. Intracellular expression of IL-1RA decreased NFkappaB reporter gene activity, indicating that endogenously expressed IL-1alpha contributes to constitutive NFkappaB activation in this HNSCC line. Expression of IL-1alpha affected survival of UM-SCC-9, inasmuch as transfection of cells with plasmid encoding IL-1alpha or IL-1RA led to the increased or decreased survival of cells cotransfected with a beta-galactosidase reporter gene, respectively. IL-1alpha was also found to promote the increased growth of UM-SCC-9 cells in vitro. We demonstrate that exogenous and endogenous IL-1alpha contributes to the transcriptional activation of NFkappaB and AP-1, to the expression of IL-8, and to cell survival and the growth of HNSCC in vitro.

Diseases/Pathways annotated by Medline MESH: Carcinoma, Squamous Cell, Head and Neck Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

IL-8 → AP-1: " IL ( interleukin)-1alpha promotes nuclear factor-kappaB and AP-1 induced IL-8 expression, cell survival, and proliferation in head and neck squamous cell carcinomas "

AP-1 ⊣ IL-1alpha: " In this study, we examined the role of IL-1alpha in the activation of NFkappaB and AP-1 , the expression of proangiogenic cytokine IL-8, and in the survival and proliferation of HNSCC cell lines "

IL-8 ⊣ IL-1alpha: " In this study, we examined the role of IL-1alpha in the activation of NFkappaB and AP-1, the expression of proangiogenic cytokine IL-8 , and in the survival and proliferation of HNSCC cell lines "

NFkappaB ⊣ IL-1alpha: " In this study, we examined the role of IL-1alpha in the activation of NFkappaB and AP-1, the expression of proangiogenic cytokine IL-8, and in the survival and proliferation of HNSCC cell lines "

IL-8 → AP-1: " In this study, we examined the role of IL-1alpha in the activation of NFkappaB and AP-1 , the expression of proangiogenic cytokine IL-8 , and in the survival and proliferation of HNSCC cell lines "

IL-8 → NFkappaB: " In this study, we examined the role of IL-1alpha in the activation of NFkappaB and AP-1, the expression of proangiogenic cytokine IL-8 , and in the survival and proliferation of HNSCC cell lines "

IL-8 ⊣ IL-1 receptor antagonist (IL-1RA): " HNSCCs were found to secrete and respond to functional IL-1alpha, in that culture supernatant from a high IL-1alpha secreting line, UM-SCC-11B, could induce secretion of cytokine IL-8 by a low IL-1alpha secreting line, UM-SCC-9 ; and the induction of IL-8 secretion could be blocked by the anti-IL-1alpha neutralizing antibody or the IL-1 receptor antagonist (IL-1RA) "

IL-1alpha → IL-8: " Furthermore, IL-1alpha could induce the expression of IL-8 through an autocrine mechanism, in that transfection of UM-SCC-9 cells with a plasmid encoding IL-1alpha resulted in the increased coexpression of IL-1alpha and IL-8 ; whereas transfection with a plasmid encoding IL-1RA lacking the secretory leader sequence led to the decreased coexpression of IL-1alpha and IL-8 "

AP-1 → IL-8: " IL-1alpha was found to induce coexpression of IL-8 through the activation of NFkappaB and AP-1 , in that mutation of the NFkappaB site within the IL-8 promoter abolished autocrine- and recombinant IL-1alpha induced IL-8 reporter gene activity, whereas mutation in AP-1 partially decreased IL-8 reporter gene activity in UM-SCC-9 cells "

IL-8 → IL-1alpha: " IL-1alpha was found to induce coexpression of IL-8 through the activation of NFkappaB and AP-1, in that mutation of the NFkappaB site within the IL-8 promoter abolished autocrine- and recombinant IL-1alpha induced IL-8 reporter gene activity, whereas mutation in AP-1 partially decreased IL-8 reporter gene activity in UM-SCC-9 cells "

NFkappaB → IL-8: " IL-1alpha was found to induce coexpression of IL-8 through the activation of NFkappaB and AP-1, in that mutation of the NFkappaB site within the IL-8 promoter abolished autocrine- and recombinant IL-1alpha induced IL-8 reporter gene activity, whereas mutation in AP-1 partially decreased IL-8 reporter gene activity in UM-SCC-9 cells "

Manually curated Databases

No curated data.