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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kawamoto, Manabu Soejima, Makoto Tochimoto, Akiko Nishimagi, Emi Kanno, Tokiko Kawaguchi, Yasushi Katsumata, Yasuhiro Kamatani, Naoyuki Hara, Masako |
| Description | Author Affiliation: Kawaguchi Y ( Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan. y-kawa@ior.twmu.ac.jp); |
| Abstract | 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 equal to 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 39 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Fibroblasts Pathology Interleukin-1 Metabolism Proteins Receptors, Interleukin-1 Scleroderma, Systemic Adaptor Proteins, Signal Transducing Animals Cell Nucleus Cells, Cultured Collagen Type I Cytology Gene Expression Regulation Immunoprecipitation Mice Models, Biological NIH 3T3 Cells Protein Binding Protein Precursors Protein Transport Genetics RNA Interference RNA, Messenger Deficiency Receptors, Interleukin-1 Type II Signal Transduction Two-Hybrid System Techniques Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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