Related Experiment Videos
Human keratinocytes constitutively produce but do not process interleukin-18
1University College London Centre for Dermatology, Jules Thorn Institute, Middlesex Hospital, Mortimer Street, London W1T 3AA, UK. j.mee@ucl.ac.uk
The British Journal of Dermatology
|August 22, 2000
Summary
Human keratinocytes constitutively produce interleukin-18 (IL-18), a key cytokine for immune responses. This IL-18 is released unprocessed, suggesting a role in skin inflammation and potential therapeutic targeting for diseases like psoriasis.
Area of Science:
- Immunology
- Dermatology
- Molecular Biology
Background:
- Interleukin-18 (IL-18) is a cytokine that enhances T-helper 1 and cytotoxic immune responses.
- IL-18 functions via a receptor complex (IL-18R/AcPL) and is regulated by IL-18 binding protein (IL-18BP).
Purpose of the Study:
- To investigate the production of IL-18 and its receptor components by human keratinocytes.
- To understand the regulation of IL-18 synthesis and release in skin cells.
Main Methods:
- Polymerase chain reaction (PCR) was used to detect IL-18 gene transcription in keratinocytes.
- Analysis of IL-18 protein levels and processing in cell lysates and supernatants.
- Detection of IL-18 receptor (IL-18R, AcPL) and IL-18BP mRNA.
Main Results:
- Human keratinocytes constitutively transcribe the IL-18 gene and produce high levels of IL-18 protein.
- IL-18 is released in an unprocessed 24-kDa form, and its production is not significantly affected by common inflammatory stimuli.
- Keratinocytes also constitutively produce IL-18R and AcPL mRNA, with inducible IL-18BP transcription upon IFN-gamma treatment.
Conclusions:
- Human keratinocytes synthesize and release IL-18 in an unprocessed state.
- Keratinocyte-derived IL-18 may modulate IFN-gamma production in cutaneous inflammatory conditions.
- IL-18 presents a potential therapeutic target for Th1-mediated inflammatory skin diseases, including psoriasis.