IL-27 regulates cytokine production as a double-edged sword in keratinocytes

Inflammaging is a subject of considerable attention, because aging is characterized by low-grade, chronic, and asymptomatic inflammation, concomitant with increased blood levels of senescence-associated secretory phenotype (SASP) factors, including IL-1, IL-6, IL-8, IL-18, and tumor necrosis factor-α (TNF-α). However, IL-27 is currently not categorized as a SASP factor, although it is known to play pleiotropic roles in inflammation. In this study, we evaluated the interaction between TNF-α and IL-27 in context of low-grade inflammation using HaCaT cells. TNF-α induced significant upregulation of the mRNA levels of IL-6 and IL-8 at the experimental concentration (~10ng/ml), while the mRNA levels of IL-1RA, IL-10, and IL-18BP were unchanged. After confirming the expression of functional IL-27 receptors in HaCaT cells, we examined the effects of IL-27 alone on cytokine expression. IL-27 alone significantly upregulated the mRNA levels of IL-10, IL-18BP and IL-6 by 1.61-fold, 1.46-fold, and 2.32-fold, respectively. In the presence of 100 ng/ml of IL-27, the mRNA levels of the anti-inflammatory cytokines IL-1RA, IL-10 and IL-18BP, were significantly upregulated upon treatment with TNF-α at the physiological concentration (1 ng/ml). Taken together, this study indicates that a high concentration of IL-27 exhibits anti-inflammatory effects in the presence of a low concentration of TNF-α, in keratinocytes, suggesting that the anti-inflammatory role of IL-27 in inflammaging may be regulated by TNF-α concentration.