Identification and Initial Characterization of Four Novel Members of the Interleukin-1 Family
Interleukin-1 (IL-1), fibroblast growth factors (FGFs), and their homologues are secreted factors that share a common β-barrel structure and act on target cells by binding to cell surface receptors with immunoglobulin-like folds in their extracellular domain. While numerous members of the FGF family...
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Veröffentlicht in: | The Journal of biological chemistry 2000-04, Vol.275 (14), p.10308-10314 |
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Sprache: | eng |
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Zusammenfassung: | Interleukin-1 (IL-1), fibroblast growth factors (FGFs), and their homologues are secreted factors that share a common β-barrel structure and act on target cells by binding to cell surface receptors with immunoglobulin-like folds in their extracellular domain. While numerous members of the FGF family have been discovered, the IL-1 family has remained small and outnumbered by IL-1 receptor homologues. From expressed sequence tag data base searches, we have now identified four additional IL-1 homologues, IL-1H1, IL-1H2, IL-1H3, and IL-1H4. Like most other IL-1/FGFs, these proteins do not contain a hydrophobic leader sequence. IL-1H4 has a propeptide sequence, while IL-1H1, IL-1H2, and IL-1H3 encode only the mature protein. Circular dichroism spectra and thermal stability analysis suggest that IL-1H1 folds similarly to IL-1ra. The novel homologues are not widely expressed in mammals. IL-1H1 is constitutively expressed only in placenta and the squamous epithelium of the esophagus. However, IL-1H1 could be inducedin vitro in keratinocytes by interferon-γ and tumor necrosis factor-α and in vivo via a contact hypersensitivity reaction or herpes simplex virus infection. This suggests that IL-1H1 may be involved in pathogenesis of immune mediated disease processes. The addition of four novel IL-1 homologues suggests that the IL-1 family is significantly larger than previously thought. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.275.14.10308 |