In late 2019, SARS-CoV-2 was detected in China and spread worldwide. In rare cases, children who were infected with COVID-19 may develop multisystem inflammatory syndrome (MIS-C), which could have higher mortality than COVID-19 itself. Therefore, diagnosis and management are critical for treatment. Specifically, most of the initial treatment options of MIS-C choose intravenous immunoglobulin (IVIG) and steroids as the first-line treatment for patients. Moreover, antagonists of some cytokines are used as potential future therapeutics. Of note, therapeutic plasmapheresis can be used as a treatment for refractory severe MIS-C. We believe that each patient, especially those with comorbid conditions, should have individualized treatment based on both multidisciplinary consensus approach and expert opinion.
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).
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