Curcumin attenuates carcinogenesis by down regulating proinflammatory cytokine interleukin-1 (IL-1α. and IL-1β) via modulation of AP-1 and NF-1L6 in lymphoma bearing mice

Interleukin-1 (IL-1 alpha and IL-1 beta) is a prototypic, potent, multifunctional proinflammatory cytokine affecting almost all cell types. Expression of IL-1 is up regulated in different tumor phenotypes and is implicated as an important factor in tumor progression via expression of metastatic, angiogenic genes and growth factors. Therefore, down regulation of expression of IL-1 may be able to inhibit cancer progression. Mechanism of transcriptional regulation of mouse IL-1 alpha is not yet reported. AP-1 binding site at - 12 to - 6 on human IL-1 alpha promotor is highly conserved in rat IL-1 alpha gene and regulates its expression. Based on in silico analysis, regions - 12 to - 6 bp is found to be conserved in human and mouse IL-1 alpha gene promotor and therefore selected to study activation of IL-1a. Further, the regions - 12 to - 6 bp in mouse IL-1 alpha gene promotor corresponding to AP-1 binding element show 3' -> 5' orientation, necessary for AP-1 binding. The present work is focused on long term effect of curcumin on expression of IL-1 alpha and IL-1 beta in liver of lymphoma bearing mice. Transcriptional regulation of IL-1 alpha and IL-1 beta was analyzed by AP-1 and NF-IL-6 respectively. Elevated expression and protein level of IL-1 alpha and IL-1 beta were found in lymphoma bearing mice compared to normal, which were significantly down regulated by curcumin treatment Similarly, curcumin treatment down regulated activation of IL-1 alpha and IL-1 beta via AP-1 and NF-IL-6 respectively. The findings conclude that curcumin. attenuates carcinogenesis by down regulating proinflammatory cytokine interleukin-1 (IL-1 alpha and IL-1 beta) via modulation of AP-1 and NF-IL6 respectively in lymphoma bearing mice. (C) 2014 Elsevier B.V. All rights reserved.