Activation of the epidermal platelet-activating factor receptor results in cytokine and cyclooxygenase-2 biosynthesis

Yong Pei, Lisa A. Barber, Robert C. Murphy, Christopher A. Johnson, Susan W. Kelley, Lady C. Dy, Richard H. Fertel, Thanh M. Nguyen, David A. Williams, Jeffrey Travers

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Recent studies suggest that the lipid mediator platelet-activating factor (PAF) is involved in keratinocyte function and skin inflammation. Indeed, PAF is found in association with inflammatory skin diseases, intradermal injections of PAF induce inflammation, and keratinocytes express functional PAF receptors (PAF-R). One mechanism by which the keratinocyte PAF-R could contribute to epidermal functions and inflammatory states would be through the synthesis of inflammatory regulators, such as PAF, PGs, and cytokines. The ability of the epidermal PAF-R to induce the synthesis of these immunomodulators was tested using a model system created by transduction of the PAF-R-negative human epidermal cell line KB with the PAF- R. Activation of this epidermal PAF-R resulted in arachidonic acid release, and the biosynthesis of PAF and PGE2. In addition, the KB PAF-R triggered increased levels of mRNA and protein for the inducible isozyme of cyclooxygenase (COX-2) as well as IL-6 and IL-8, both of which have been implicated in skin inflammatory processes. Studies with the human keratinocyte-derived epidermal cell line HaCaT revealed that activation of the endogenous PAF-R led to the increased accumulation of COX-2, IL-6, and IL-8 mRNA similar to that seen with the KB PAF-R model system. Finally, treatment of HaCaT keratinocytes with IL-8 resulted in PAF biosynthesis, indicating the existence of a positive feedback loop between IL-8 and PAF in epidermal cells. These studies suggest involvement of PAF and the PAF-R in the epidermal cytokine network.

Original languageEnglish
Pages (from-to)1954-1961
Number of pages8
JournalJournal of Immunology
Volume161
Issue number4
StatePublished - Aug 15 1998

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Platelet Activating Factor
Cyclooxygenase 2
Cytokines
Keratinocytes
Interleukin-8
platelet activating factor receptor
Interleukin-6
Inflammation
Cell Line
Intradermal Injections
Messenger RNA
Skin
Immunologic Factors
Dinoprostone
Skin Diseases
Arachidonic Acid

ASJC Scopus subject areas

  • Immunology

Cite this

Pei, Y., Barber, L. A., Murphy, R. C., Johnson, C. A., Kelley, S. W., Dy, L. C., ... Travers, J. (1998). Activation of the epidermal platelet-activating factor receptor results in cytokine and cyclooxygenase-2 biosynthesis. Journal of Immunology, 161(4), 1954-1961.

Activation of the epidermal platelet-activating factor receptor results in cytokine and cyclooxygenase-2 biosynthesis. / Pei, Yong; Barber, Lisa A.; Murphy, Robert C.; Johnson, Christopher A.; Kelley, Susan W.; Dy, Lady C.; Fertel, Richard H.; Nguyen, Thanh M.; Williams, David A.; Travers, Jeffrey.

In: Journal of Immunology, Vol. 161, No. 4, 15.08.1998, p. 1954-1961.

Research output: Contribution to journalArticle

Pei, Y, Barber, LA, Murphy, RC, Johnson, CA, Kelley, SW, Dy, LC, Fertel, RH, Nguyen, TM, Williams, DA & Travers, J 1998, 'Activation of the epidermal platelet-activating factor receptor results in cytokine and cyclooxygenase-2 biosynthesis', Journal of Immunology, vol. 161, no. 4, pp. 1954-1961.
Pei Y, Barber LA, Murphy RC, Johnson CA, Kelley SW, Dy LC et al. Activation of the epidermal platelet-activating factor receptor results in cytokine and cyclooxygenase-2 biosynthesis. Journal of Immunology. 1998 Aug 15;161(4):1954-1961.
Pei, Yong ; Barber, Lisa A. ; Murphy, Robert C. ; Johnson, Christopher A. ; Kelley, Susan W. ; Dy, Lady C. ; Fertel, Richard H. ; Nguyen, Thanh M. ; Williams, David A. ; Travers, Jeffrey. / Activation of the epidermal platelet-activating factor receptor results in cytokine and cyclooxygenase-2 biosynthesis. In: Journal of Immunology. 1998 ; Vol. 161, No. 4. pp. 1954-1961.
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abstract = "Recent studies suggest that the lipid mediator platelet-activating factor (PAF) is involved in keratinocyte function and skin inflammation. Indeed, PAF is found in association with inflammatory skin diseases, intradermal injections of PAF induce inflammation, and keratinocytes express functional PAF receptors (PAF-R). One mechanism by which the keratinocyte PAF-R could contribute to epidermal functions and inflammatory states would be through the synthesis of inflammatory regulators, such as PAF, PGs, and cytokines. The ability of the epidermal PAF-R to induce the synthesis of these immunomodulators was tested using a model system created by transduction of the PAF-R-negative human epidermal cell line KB with the PAF- R. Activation of this epidermal PAF-R resulted in arachidonic acid release, and the biosynthesis of PAF and PGE2. In addition, the KB PAF-R triggered increased levels of mRNA and protein for the inducible isozyme of cyclooxygenase (COX-2) as well as IL-6 and IL-8, both of which have been implicated in skin inflammatory processes. Studies with the human keratinocyte-derived epidermal cell line HaCaT revealed that activation of the endogenous PAF-R led to the increased accumulation of COX-2, IL-6, and IL-8 mRNA similar to that seen with the KB PAF-R model system. Finally, treatment of HaCaT keratinocytes with IL-8 resulted in PAF biosynthesis, indicating the existence of a positive feedback loop between IL-8 and PAF in epidermal cells. These studies suggest involvement of PAF and the PAF-R in the epidermal cytokine network.",
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