α-Fetoprotein as a modulator of the pro-inflammatory response of human keratinocytes

A. I. Potapovich, S. Pastore, V. A. Kostyuk, D. Lulli, V. Mariani, C. De Luca, E. I. Dudich, L. G. Korkina

Research output: Contribution to journalArticlepeer-review

Abstract

Background and purpose: The immunomodulatory effects of α-fetoprotein (AFP) on lymphocytes and macrophages have been described in vitro and in vivo. Recombinant forms of human AFP have been proposed as potential therapeutic entities for the treatment of autoimmune diseases. We examined the effects of embryonic and recombinant human AFP on the spontaneous, UVA- and cytokine-induced pro-inflammatory responses of human keratinocytes. Experimental approach: Cultures of primary and immortalized human keratinocytes (HaCaT) and human blood T lymphocytes were used. The effects of AFP on cytokine expression were studied by bioplexed ELISA and quantitative reverse transcriptase polymerase chain reaction assay. Kinase and nuclear factor kappa B (NFKB) phosphorylation were quantified by intracellular ELISA. Nuclear activator protein 1 and NFKB DNA binding activity was measured by specific assays. Nitric oxide and H 2O 2 production and redox status were assessed by fluorescent probe and biochemical methods. Key results: All forms of AFP enhanced baseline expression of cytokines, chemokines and growth factors. AFP dosedependently increased tumour necrosis factor alpha-stimulated granulocyte macrophage colony stimulating factor and interleukin 8 expression and decreased tumour necrosis factor alpha-Induced monocyte chemotactic protein 1 and IP-10 (interferon gamma-produced protein of 10 kDa) expression. AFP induced a marked activator protein 1 activation in human keratinocytes. AFP also increased H 2O 2 and modulated nitrite/nitrate levels in non-stimulated keratinocytes whereas it did not affect these parameters or cytokine release from UVA-stlmulated cells. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and Aktl but not NFKB was activated by AFP alone or by its combination with UVA. Conclusions and Implications: Exogenous AFP induces activation of human keratinocytes, with de novo expression of a number of pro-inflammatory mediators and modulation of their pro-Inflammatory response to cytokines or UVA. AFP may modulate Inflammatory events In human skin.

Original languageEnglish
Pages (from-to)1236-1247
Number of pages12
JournalBritish Journal of Pharmacology
Volume158
Issue number5
DOIs
Publication statusPublished - 2009

Keywords

  • α-fetoprotein
  • AP-1
  • Chemokines
  • Cytokines
  • Human keratinocytes
  • UVA

ASJC Scopus subject areas

  • Pharmacology

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