Early molecular events in the induction phase of contact sensitivity.
To assess changes in epidermis-derived cytokine mRNA levels early in the afferent phase of allergic contact sensitivity, total epidermal mRNA was analyzed at various times after painting skin with haptens. We used a sensitive reverse transcriptase-polymerase chain reaction technique to quantitatively compare the regulation patterns of the following mRNAs: class II major histocompatibility complex I-A alpha, tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 1 alpha, IL-1 beta, interferon (IFN) gamma, granulocyte/macrophage colony-stimulating factor, IFN-induced protein 10, and macrophage inflammatory protein 2. Enhanced Langerhans cell-derived IL-1 beta mRNA signals were detected as early as 15 min after skin painting with allergens. TNF-alpha, IFN-gamma, and granulocyte/macrophage colony-stimulating factor mRNAs were found to be upregulated after application of allergens, irritant, and tolerogens, but class II major histocompatibility complex I-A alpha, IL-1 alpha, IL-1 beta, IFN-induced protein 10, and macrophage inflammatory protein 2 mRNAs were upregulated only after allergen painting. Depletion of specific cell populations demonstrated that Langerhans cells were the primary source of the IL-1 beta and class II major histocompatibility complex I-A alpha mRNAs, keratinocytes were the primary source of TNF-alpha, IL-1 alpha, IFN-induced protein 10, and macrophage inflammatory protein 2, and infiltrating T lymphocytes were the source of IFN-gamma. Relevance of the molecular findings was demonstrated by the identification of biologically active IL-1 alpha and immunoreactive TNF-alpha in culture supernatants. These studies demonstrate that Langerhans cell-derived and certain keratinocyte-derived cytokine mRNAs are selectively upregulated by allergens in the very early afferent phase of contact sensitivity.
Enk
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AH
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Katz
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D000485:Allergens / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003877:Dermatitis, Contact / Q000503:physiopathology*; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006241:Haptens / Q000276:immunology; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000032:analysis; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015846:Monokines / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000503:physiopathology*; D013997:Time Factors
D000485:Allergens; D000911:Antibodies, Monoclonal; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D016207:Cytokines; D006241:Haptens; D007375:Interleukin-1; D015846:Monokines; D012333:RNA, Messenger; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor