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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Intracellular IL-1{alpha}-binding proteins contribute to biological functions of endogenous IL-1{alpha} in systemic sclerosis fibroblasts.

The aberrant production of precursor IL-1alpha (pre-IL-1alpha) in skin fibroblasts that are derived from systemic sclerosis (SSc) is associated with the induction of IL-6 and procollagen, which contributes to the fibrosis of SSc. However, little is understood about how intracellular pre-IL-1alpha regulates the expression of the other molecules in fibroblasts. We report here that pre-IL-1alpha can form a complex with IL-1alpha-binding proteins that is translocated into the nuclei of fibroblasts. Immunoprecipitation that used anti-human IL-1alpha Ab and (35)S-labeled nuclear extracts of fibroblasts showed three specific bands ( approximately 31, 35, and 65 kDa). The 31-kDa molecule was identified as pre-IL-1alpha, and the 35- and 65-kDa molecules might be pre-IL-1alpha-binding proteins. A partial sequencing for the 10 aa from the N-terminals of the molecules showed 100% homology for HAX-1 (HS1-associated protein X-1) and IL-1 receptor type II (IL-1RII). Suppression of the genes of HAX-1 or IL-1RII induced the inhibitory effects of IL-1 signal transduction, including production of IL-6 and procollagen, by fibroblasts. In particular, pre-IL-1alpha was not translocated into the nucleus by an inhibition of HAX-1. These findings reveal that nuclear localization of pre-IL-1alpha depends on the binding to HAX-1 and that biological activities might be elicited by the binding to both HAX-1 and IL-1RII in SSc fibroblasts.[1]

References

  1. Intracellular IL-1{alpha}-binding proteins contribute to biological functions of endogenous IL-1{alpha} in systemic sclerosis fibroblasts. Kawaguchi, Y., Nishimagi, E., Tochimoto, A., Kawamoto, M., Katsumata, Y., Soejima, M., Kanno, T., Kamatani, N., Hara, M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
 
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