Transcription and secretion of interleukin-1β and HMGB1 in keratinocytes exposed to stimulations mimicking common inflammatory damage

Abstract

Objective: Interleukin-1β (IL-1β) and high-mobility group box 1 (HMGB1) are widely known damage-associated molecular patterns (DAMPs). However, their expression and secretion in different skin diseases, especially in inflammatory skin disorders, remain to be further elucidated. This study was performed to explore and compare the transcriptional and secretory levels of IL-1β and HMGB1 in keratinocytes under three types of stimulation: ultraviolet B (UVB) irradiation; co-stimulation by tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) (simulation of T helper 1 cell inflammatory challenge); and psoriasis-like stimulation by M5, a mixture of five proinflammatory cytokines. Methods: We used quantitative reverse-transcription polymerase chain reaction to determine the transcription levels of IL-1β and HMGB1. Western blotting and enzyme-linked immunosorbent assay were used to detect the secretion levels of IL-1β and HMGB1. The results were statistically analyzed by t test. Results: A rapid transcriptional and secretory response of IL-1β from keratinocytes occurred in all three types of stimulation mimicking common inflammatory environments (P < 0.05). Transcription of HMGB1 was inhibited in all three types of stimulation (P < 0.05), but secretion was increased after exposure to UVB irradiation and co-stimulation by TNF-α and IFN-γ (P < 0.05). We observed no change in the secretion level of HMGB1 after treatment with M5 (P = 0.196 > 0.05). Conclusion: IL-1β is a critical cytokine for the immunomodulatory functions of keratinocytes in inflammatory responses. In this study, keratinocytes restrained transcription of HMGB1 when the secretion of HMGB1 was induced in certain stimulations (e.g., by UVB exposure or stimulation by TNF-α and IFN-γ).