Human growth factor (huGRO), interleukin-8 (IL-8) and interferon-γ-inducible protein (γ-IP-10) gene expression in cultured normal human keratinocytes

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Abstract
HuGRO, IL-8 and γ-IP-10 belong to a recently described superfamily of genes encoding a group of cytokines with inflammatory, growth regulating and/or leukocyte chemotactic properties (chemokines). We studied huGRO, IL-8 and γ-IP-10 gene expression in unstimulated and stimulated (TNFα, INFγ, TNFα + IFNγ, IL-1Β, PMA and LPS) normal human keratinocytes by Northern blot analysis. The mRNA for none of the three chemokines was detectable in unstimulated keratinocytes, but considerably elevated levels of huGRO and IL-8 mRNA, but not of γ-IP-10 mRNA, were found in the presence of cycloheximide, indicating that huGRO and IL-8 mRNA, but not γ-IP-10 mRNA, are constitutively produced. γ-IP-10 mRNA was exclusively induced by IFNγ, with a strong and transient rise between 8 and 18 h, and superinduced by the combination of IFNγ and TNFα, indicating marked synergism. Both huGRO and IL-8 mRNA were induced by TNFα and PMA (a strong and transient rise between 2 and 8 h), but not by IFNγ or LPS. The combination of TNFα and IFNγ did not show a synergistic effect. In addition, IL-1Β transiently upregulated huGRO mRNA but failed to induce IL-8 mRNA. Using specific oligonucleotides for α, Β and γ huGRO, TNFα was found to induce all three forms, α and Β to an equal extent and γ to a lesser extent. Our results indicate that there is stimulus-specific transcription of these early response genes which may have important implications for the modulation of cutaneous inflammatory processes.