Curcumin attenuates carcinogenesis by down regulating proinflammatory cytokine interleukin-1 (IL-1α and IL-1β) via modulation of AP-1 and NF-IL6 in lymphoma bearing mice

Interleukin-1 (IL-1α and IL-1β) 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-1α is not yet reported. AP-1 binding site at -12 to -6 on human IL-1α promotor is highly conserved in rat IL-1α gene and regulates its expression. Based on in silico analysis, regions -12 to -6bp is found to be conserved in human and mouse IL-1α gene promotor and therefore selected to study activation of IL-1α. Further, the regions -12 to -6bp in mouse IL-1α 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-1α and IL-1β in liver of lymphoma bearing mice. Transcriptional regulation of IL-1α and IL-1β was analyzed by AP-1 and NF-IL-6 respectively. Elevated expression and protein level of IL-1α and IL-1β 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-1α and IL-1β via AP-1 and NF-IL-6 respectively. The findings conclude that curcumin attenuates carcinogenesis by down regulating proinflammatory cytokine interleukin-1 (IL-1α and IL-1β) via modulation of AP-1 and NF-IL6 respectively in lymphoma bearing mice.