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Characterization of immunoregulatory cytokines produced by epidermal cells.

Abstract：

:The epidermis has been identified as an important site for the initiation of immunological events. In addition to the macrophage-like Langerhans cells, keratinocytes within the epidermal cells have been shown to act as immunoregulatory cells through the secretion of cytokines such as epidermal cell-derived thymocyte-activating factor (ETAF) and interleukin 3. Epidermal cell-derived interleukin 3 (EC IL-3), like lymphocyte-derived IL-3, induced the proliferation of IL-3-dependent mast cell-like cell lines. Biochemically, EC IL-3 was a heat-stable protein with a molecular weight of approximately 30 kD. Upon chromatofocusing, EC IL-3 exhibited three isoelectric points, at pI 7.8, 7.4, and 7.1. Furthermore, an antiserum against IL-3 neutralized EC IL-3 activity, suggesting that the molecules are closely related and share similar epitopes. ETAF-like macrophage-derived interleukin 1 (IL-1) is a low molecular weight protein with a multiplicity of amplifying effects on immunological and inflammatory reactions. Thus BALB/c mice were immunized with partially purified IL-1, and immune spleen cells were hybridized with plasmocytoma cells. Supernatants of the hybridoma cultures were screened for their capacity to inhibit IL-1-induced thymocyte proliferation. After expansion and cloning, one clone was selected for ascitic antibody production. The monoclonal anti-IL-1 antibody inhibited both the IL-1-dependent thymocyte and the fibroblast proliferation. Furthermore, the antibody blocked murine and human ETAF activity, suggesting that ETAF and IL-1 share antigenically similar domains. Moreover, by using the monoclonal antibody bound to Staphylococcus aureus cells, it was possible to immunoprecipitate IL-1. In contrast, anti-IL-1 antibody did not inhibit IL-2 or IL-3 activity. These findings demonstrate that the production of immunoregulatory cytokines is not confined to cells of the immune system and that keratinocytes through the production of ETAF and EC IL-3 may mediate inflammatory and hypersensitivity reactions. Furthermore, the monoclonal anti-IL-1 antibody may provide a useful tool for the development of new immunoassays to detect IL-1/ETAF and thereby facilitate the investigation of the role of these cytokines during the pathogenesis of inflammatory diseases.

journal_name

Scand J Immunol

journal_title

Scandinavian journal of immunology

authors

Luger TA,Köck A,Danner M

doi

10.1111/j.1365-3083.1985.tb01832.x

subject

Has Abstract

pub_date

1985-05-01 00:00:00

pages

455-62

issue

eissn

0300-9475

issn

1365-3083

journal_volume

pub_type

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Characterization of immunoregulatory cytokines produced by epidermal cells.