{'fraction_non_alphanumeric': 0.05150976909413854, 'fraction_numerical': 0.03493191237418591, 'mean_word_length': 4.8075601374570445, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
IL-27 skews TNF-alpha-induced inflammatory microenvironment in keratinocytes

Inflammaging has received 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-alpha (TNF-alpha). On the other hand, IL-27 is not categorized as SASP factors though it is known that IL-27 has pleiotropic roles in inflammation. Here, we evaluated the interaction between TNF-alpha and IL-27 in the context of low-grade inflammation by using in HaCaT cells. TNF-alpha induced significant upregulation of IL-6 and IL-8 through the experimental concentrations (~10 ng/ml) of TNF-alpha, while the mRNA expression levels of IL-1RA, IL-10 and IL-18BP were unchanged. After confirming the expression of IL-27 receptor in HaCaT cells, we examined the effects of IL-27 alone on the cytokine expression. IL-27 alone significantly enhanced mRNA expression levels of IL-10 and IL-18BP by 1.61-fold and 1.46-fold, respectively, and also enhanced mRNA expression levels of IL-6 by 2.32-fold. In the presence of 100 ng/ml IL-27, the expression levels of anti-inflammatory cytokines, IL-1RA, IL-10 and IL-18BP, were significantly upregulated with the treatment of a physiological concentration (1 ng/ml) TNF-alpha. Taken together, a high concentration of IL-27 exhibits anti-inflammatory effects in the presence of a low concentration of TNF-alpha when keratinocytes are the recipient of IL-27 signaling, suggesting the anti-inflammatory roles of IL-27 in inflammaging may be regulated by TNF-alpha concentration.