Synthesis of Complement Components C3 and Factor B in Human Keratinocytes is Differentially Regulated by Cytokines
Open accessAbstract
The complement system plays an important part in host defense and inflammation. Locally synthesized complement may perform these functions at tissue and organ level. In skin the keratinocyte is the major cell type, it is known to produce two soluble complement components, C3 and factor B. In this study we investigated the regulation of synthesis of these components in foreskin keratinocytes by cytokines. Human keratinocytes were cultured in the presence of supernatant of activated peripheral blood mononuclear cells, interleukin-1alpha, interleukin-2, interleukin-6, transforming growth factor-beta1, tumor necrosis factor-alpha, or interferon-gamma. C3 and factor B proteins were measured in culture supernatant by enzyme-linked immunosorbent assay and C3 and factor B transcripts in harvested cells by reverse transcriptase-polymerase chain reaction. Cultured keratinocytes constitutively produced C3 and factor B. Supernatant of activated mononuclear cells upregulated C3 and factor B production by 27- and 15-fold, respectively. interleukin-1alpha, interferon-gamma, and tumor necrosis factor-alpha upregulated C3 synthesis by 7-, 8-, and 22-fold, and interleukin-1alpha, interleukin-6, and interferon-gamma upregulated factor B synthesis by 3-, 3-, and 34-fold, respectively. Tumor necrosis factor-alpha induced production of C3 and interferon-gamma induced production of factor B were inhibited by cycloheximide. Cytokine induced upregulation of C3 and factor B proteins was always associated with the upregulation of levels of C3 and factor B mRNA. This indicated that, as expected, cytokine-induced enhancement in C3 and factor B levels was due to an increase in synthesis rather than their possible release from intracellular stores. In conclusion, synthesis of C3 and factor B in keratinocytes is regulated by some cytokines, known to be produced by inflammatory cells and keratinocytes.
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The Interplay of Complements and their Regulators in the Human Body
Khan, R. M. A., Musharraf, M., Javed, S., Jamil, H., Iqbal, M. S., Muhammad, F., Yaseen, M., & Kazmi, K. (2024) · Journal of Microbiological Sciences · doi:10.38211/jms.2024.03.68
Management of acute infusion-related reactions in AAV gene therapy guided by mechanistic insight
Sullivan, B. A., Collis, R., Cahayag, R., Lopez, H. M., Baker, M. G., Kakkis, E., Rahman, S., Bega, D., Breilyn, M. S., Mitchell, J. J., et al. (2026) · Molecular Therapy Advances · doi:10.1016/j.omta.2026.201840
- Authors
- Pasch, M. C., van den Bosch, N. H. A., Bos, J. D., Asghar, S. S., & Daha, M. R.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Leiden University (NL)
- Corresponding author
- Pasch, Marcel C.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2000-01
- Volume
- 114
- Issue
- 1
- Pages
- 78-82
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2129010323
- Cited by
- 77
- References
- 24
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 7 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 1
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Keywords
- complement C3, factor B, keratinocytes, cytokine regulation, interleukin-1 alpha, interferon-gamma, TNF-α, interleukin-6, TGF-β1, interleukin-2, skin inflammation, mRNA expression, cycloheximide
- MeSH terms
- Cells, Cultured, Child, Preschool, Complement C3, Cycloheximide, Humans, Monocytes, Complement Factor B, Protein Synthesis Inhibitors, Protein Biosynthesis, Keratinocytes, Up-Regulation, Cytokines
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