Cloning and Characterization of IL-1HY2, a Novel Interleukin-1 Family Member

Abstract

The interleukin-1 (IL-1) family members play an important role in the process of inflammation and host defense. We describe here the identification and characterization of a novel member of the IL-1 family, IL-1HY2. The human IL-1HY2 protein shares significant amino acid sequence similarity (37%) with the IL-1 receptor antagonist and has a predicted three-dimensional structure similar to that of the IL-1 receptor antagonist. The IL-1HY2 gene is located in close proximity to other IL-1 family genes on human chromosome 2, and the genomic organization of the IL-1HY2 gene is highly conserved with other IL-1 family members. IL-1HY2 protein is secreted from mammalian cells, and the purified recombinant IL-1HY2 protein binds soluble IL-1 receptor type I. IL-1HY2 is expressed in human skin, spleen, and tonsil. Immunohistochemical analysis showed that the IL-1HY2 protein is expressed in the basal epithelia of skin and in proliferating B cells of the tonsil. These data suggest that IL-1HY2 is a novel IL-1 family member and that it may participate in a network of IL-1 family members to regulate adapted and innate immune responses.

A complex of the IL-1 homologue IL-1F7b and IL-18-binding protein reduces IL-18 activity

“…Six members of the IL-1 gene family have been discovered from expressed sequence tag database searches (3)(4)(5)(6)(7)(8)(9)(10). These proteins share a common ␤-barrel pattern consisting of 12 ␤-strands and significant amino acid homology with the IL-1 receptor antagonist (IL-1Ra), IL-1␤, and IL-18.…”

Functional Genomic Analysis of Type II IL-1β Decoy Receptor: Potential for Gene Therapy in Human Arthritis and Inflammation

“…The recent identification of closely related ligands that also bind to the IL-1␤R contributes to the complexity of this family of proteins. These include new receptor antagonists for IL-1␤, such as IL-1HY1 and IL-1HY2, and other novel ligands, such as IL-1H1-H4 (22)(23)(24)(25). IL-1 activity, which is usually imparted by IL-1␣ and IL-1␤ via the IL-1R, seems to be a tightly regulated process.…”

Identification of a Critical Ig-Like Domain in IL-18 Receptor α and Characterization of a Functional IL-18 Receptor Complex

“…I nterleukin-18 is a member of the IL-1 family and shares the common structure of IL-1 family members (1)(2)(3). IL-18 also shares cell signaling with IL-1 family members, recruiting IL-1R-associated kinases, the formation of the IL-1R-associated kinase complexes with the TNF receptor-associated factor-6, and activation of the cascade of I B␣/NF-B (4 -6).…”

“…Both chains of the IL-18R belong to the IL-1R family and consist of three Ig-like domains in the extracellular region (17)(18)(19). IL-18-binding protein (IL-18BP) 3 is not a part of the IL-18 signaling complex, but, rather, antagonizes IL-18 activity (2,20). It is a unique, secreted receptor-like molecule and consists of a single Ig-like domain.…”