Transcription and Secretion of Interleukin-1β and HMGB1 in Keratinocytes Exposed to Stimulations Mimicking Common Inflammatory Damages
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 3 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 5 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 3 types of stimulation mimicking common inflammatory environments (
P < 0.05). Transcription of HMGB1 was inhibited in all 3 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).
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 (eg, by UVB exposure or stimulation by TNF-α and IFN-γ).
damage-associated molecular patterns、interleukin-1β、high-mobility group box 1、keratinocytes、inflammatory skin disorders
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National Natural Science Foundation of China81972952, 81872531, 82173438, and 82273550;Nanjing Incubation Program for National Clinical Research Center2019060001;CAMS Innovation Fund for Medical Sciences2021-1-I2M-059, 2017-I2M-1-017;Jiangsu Province FoundationLGY2018095, WSW-016;PhD Programs Foundation of Ministry of Education of ChinaNo. 20131106120046
2024-01-30（万方平台首次上网日期，不代表论文的发表时间）
共9页
121-129
