Expression of terminal complement components by human keratinocytes

Area of Science:

• Immunology
• Dermatology
• Complement System Biology

Background:

• Human keratinocytes are key players in the skin's immune system, producing cytokines and complement proteins.
• Previous studies identified keratinocyte synthesis of complement components C3, factor B, factor H, and factor I.
• The synthesis and regulation of terminal complement components by keratinocytes remained largely uninvestigated.

Purpose of the Study:

• To investigate the synthesis of terminal complement components (C5-C9) by human keratinocytes.
• To examine the regulatory effects of specific cytokines (IL-1alpha, IL-2, IL-6, TGF-beta1, TNF-alpha, IFN-gamma) on terminal complement component synthesis.

Main Methods:

• Analysis of mRNA expression for complement components C5-C9 in human keratinocytes.
• Detection of secreted complement proteins C5-C9 in keratinocyte culture supernatants.
• Treatment of keratinocytes with various cytokines to assess regulatory impacts on complement synthesis.

Main Results:

• Human keratinocytes constitutively express mRNA for C5, C7, C8gamma, and C9, but not C6, C8alpha, or C8beta.
• Keratinocytes secrete C7 and C9, but not C5, C6, or C8.
• Only TNF-alpha significantly upregulated the production of C9 among the tested cytokines.

Conclusions:

• Human keratinocytes synthesize select terminal complement components, including C7 and C9.
• The synthesis of C9 by keratinocytes is subject to regulation, notably by TNF-alpha.
• These findings expand the understanding of keratinocytes' role in the complement system within the skin immune response.