Role of fibroblasts in the regulation of proinflammatory interleukin IL-1, IL-6 and IL-8 levels induced by keratinocyte-derived IL-1

Autor: Ingeborg L.A. Boxman, Cindy Ruwhof, Clemens W.G.M. Löwik, Maria Ponec, Otto C. Boerman
Rok vydání: 1996
Předmět:
Keratinocytes
medicine.medical_specialty
media_common.quotation_subject
medicine.medical_treatment
Dermatology
Biology
3T3 cells
Proinflammatory cytokine
Mice
Internal medicine
medicine
Animals
Humans
RNA
Messenger
Interleukin 8
Fibroblast interaction
Internalization
Fibroblast
GeneralLiterature_REFERENCE(e.g.
dictionaries
encyclopedias
glossaries)
Cells
Cultured
media_common
Interleukin-6
Development of radiopharmaceuticals for diagnosis and therapy of pathological processes
Interleukin-8
Receptors
Interleukin-1
3T3 Cells
General Medicine
Fibroblasts
Cell biology
Squamous carcinoma
Ontwikkeling van radiofarmaca ten behoeve van diagnose en behandeling van ziekteprocessen
medicine.anatomical_structure
Cytokine
Endocrinology
Epidermal Cells
Culture Media
Conditioned
Female
Epidermis
Inflammation Mediators
IL-1 receptor
Keratinocyte
Interleukin-1
Zdroj: Archives of Dermatological Research, 288, pp. 391-398
Archives of Dermatological Research, 288, 391-398
Archives of Dermatological Research 288 (1996) 7
Archives of Dermatological Research, 288, 7, pp. 391-398
Archives of Dermatological Research, 288(7), 391-398
ISSN: 0340-3696
Popis: In the epidermis, the keratinocytes are the first cells to be encountered by external stimuli and they are able to promote the inflammatory response by increased production and release of various cytokines. In their turn, these cytokines may directly affect the production of proinflammatory cytokines in human dermal fibroblasts. In addition, in both epithelial and mesenchymal cells cytokine production may be modulated by their mutual interaction, and thereby regulate the inflammatory response. The present study aimed to examine the role of fibroblasts in the regulation of proinflammatory IL-1, IL-6 and IL-8 levels induced by keratinocyte-derived IL-1. The data show that in fibroblasts exposed to conditioned media derived from cultures of normal human keratinocytes or squamous carcinoma cells (SCC-4), both the IL-8 and IL-6 mRNA expression as well as protein production were elevated. In addition, it was shown that these effects were induced by IL-1 alpha. The IL-1 alpha-induced increase in IL-8 and IL-6 production, both on the protein level as well as on the mRNA level, were concentration dependent and occurred almost simultaneously. While the induction of IL-6 and IL-8 occurred simultaneously, the IL-6 mRNA remained elevated for longer. In contrast to increased IL-6 and IL-8 production the IL-1 alpha levels markedly decreased upon culturing of fibroblasts in keratinocyte-derived conditioned medium. From internalization experiments it could be concluded that binding of IL-1 to IL-1 receptors, and its subsequent internalization and intracellular degradation is the most likely mechanism involved in the reduction of IL-1 levels by fibroblasts. Comparing the rate of IL-1 reduction in the presence of various cell types indicated that the rate of IL-1 reduction is directly related to the number of IL-1 receptors found on these cell types. In conclusion, these results indicate that the release of IL-1 alpha by activated keratinocytes may act as an inducer of IL-8 and IL-6 production in neighbouring fibroblasts. This may be an important pathway for the amplification of the inflammatory response. The amounts of both cytokines produced by fibroblasts were at least two to three orders of magnitude higher than those produced by keratinocytes, suggesting an important role of fibroblasts in the general inflammatory response. Furthermore, fibroblasts might be involved in turning off this inflammatory response by reducing IL-1 levels, most likely via IL-1 receptor-mediated uptake.
Databáze: OpenAIRE
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