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 beta-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 induced in vitro in keratinocytes by interferon-gamma and tumor necrosis factor-alpha 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.
Kumar
S
S
Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. Sanjay_Kumar@SBPHRD.COM
McDonnell
P C
PC
Lehr
R
R
Tierney
L
L
Tzimas
M N
MN
Griswold
D E
DE
Capper
E A
EA
Tal-Singer
R
R
Wells
G I
GI
Doyle
M L
ML
Young
P R
PR
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002942:Circular Dichroism; D003001:Cloning, Molecular; D004848:Epithelium / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006561:Herpes Simplex / Q000276:immunology; D018259:Herpesvirus 1, Human; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010081:Oxazolone / Q000494:pharmacology; D017510:Protein Folding; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D007375:Interleukin-1; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins; D010081:Oxazolone