GRO-alpha mRNA is selectively overexpressed in psoriatic epidermis and is reduced by cyclosporin A in vivo, but not in cultured keratinocytes.
Interleukin (IL)-8 and gro peptides are members of the intercrine-alpha family of chemotaxins known to be present in biologically active form in psoriasis lesions. However, the relative contribution of the three different gro genes to the expression of this material is unknown, as is the stimulus for gro overexpression in psoriatic lesions. To address these questions, Northern blot and semiquantitative polymerase chain reaction analysis were performed on RNA extracted from keratome biopsies of normal skin, untreated plaques of psoriasis, or plaques treated for 1 week with low-dose cyclosporin A (CsA). Northern blot analysis revealed a significant correlation between gro and IL-8 mRNA levels in psoriasis lesions from 26 different individuals (r = 0.61, p = 0.0009), and overexpression of gro was markedly reduced by CsA prior to detectable clinical improvement (79.3%, p = 0.01, n = 22). To determine which form(s) of gro were overexpressed in psoriatic lesions, total keratome RNA (1 microgram) was analyzed by semiquantitative reverse transcription-polymerase chain reaction (SQRT-PCR). In five patients known to markedly overexpress gro and IL-8 mRNAs by Northern blotting, gro-alpha was approximately six times more abundant than gro-beta, and 25 times more abundant than gro-gamma. In cultured human keratinocytes, all three forms of gro mRNA were increased by IL-1 alpha or by interferon (IFN)-gamma plus tumor necrosis factor (TNF)-alpha. However, in contrast to the situation in vivo, CsA had no inhibitory effect on cytokine-stimulated gro expression in cultured keratinocytes. Taken together, these results demonstrate that the gro-alpha gene is selectively overexpressed in psoriatic lesions and strongly suggest that overexpression of gro is a keratinocyte response to activated T cells in psoriasis.
Kojima
T
T
Chiba University, Japan.
Cromie
M A
MA
Fisher
G J
GJ
Voorhees
J J
JJ
Elder
J T
JT
D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D016572:Cyclosporine / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D007536:Isomerism; D015603:Keratinocytes / Q000187:drug effects*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D012867:Skin / Q000187:drug effects
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016572:Cyclosporine