HUMAN GROWTH-FACTOR (HUGRO), INTERLEUKIN-8 (IL-8) AND INTERFERON-GAMMA-INDUCIBLE PROTEIN (GAMMA-I-IP-10) GENE-EXPRESSION IN CULTURED NORMALHUMAN KERATINOCYTES

HuGRO, IL-8 and gamma-IP-10 belong to a recently described superfamily of genes encoding a group of cytokines with inflammatory, growth regu lating and/or leukocyte chemotactic properties (chemokines). We studie d huGRO, IL-8 and gamma-IP-10 gene expression in unstimulated and stim ulated (TNF alpha, INF gamma, TNF alpha + IFN gamma, IL-1 beta, PMA an d LPS) normal human keratinocytes by Northern blot analysis. The mRNA for none of the three chemokines was detectable in unstimulated kerati nocytes, but considerably elevated levels of huGRO and IL-8 mRNA, but not of gamma-IP-10 mRNA, mere found in the presence of cycloheximide, indicating that huGRO and IL-8 mRNA, but not gamma-IP-10 mRNA, are con stitutively produced. gamma-IP-10 mRNA was exclusively induced by IFN gamma, with a strong and transient rise between 8 and 18 h, and superi nduced by the combination of IFN gamma and TNF alpha, indicating marke d synergism. Both huGRO and IL-8 mRNA were induced by TNF alpha and PM A (a strong and transient rise between 2 and 8 h), but not by IFN gamm a or LPS. The combination of TNF alpha and IFN gamma did not show a sy nergistic effect. In addition, IL-1 beta transiently upregulated huGRO mRNA but failed to induce IL-8 mRNA. Using specific oligonucleotides for alpha, beta and gamma huGRO, TNF alpha was found to induce all thr ee forms, alpha and beta to an equal extent and gamma to a lesser exte nt. Our results indicate that there is stimulus-specific transcription of these early response genes which may have important implications f or the modulation of cutaneous inflammatory processes.