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| Content Provider | PubMed Central |
|---|---|
| Author | Kim, Busun Lee, Youngmin Kim, Eunsom Kwak, Areum Ryoo, Soyoon Bae, Seung Hyeon Azam, Tania Kim, Soohyun Dinarello, Charles A. |
| Copyright Year | 2013 |
| Abstract | Among the 11 members of the IL-1 family cytokines, the precursors of IL-1α, IL-1β, and IL-33 have relatively long N-terminal pro-sequences of approximately 100 amino acid residues prior to the N-terminus of the mature forms. Compared to the mature forms secreted from the cell, 80–90% of the primary translation product is in the intracellular compartment in the precursor form. However, the precursors are readily released from cells during infections but also with non-infectious conditions such a hypoxia and trauma. In this setting, the precursors act rapidly as “alarmins” in the absence of a processing mechanism to remove the pro-sequence and generate a mature form. In the case of IL-1α, the release of the precursor activates adjacent cells via receptor-mediated signaling. However, there are no data comparing the specific activity of the IL-1α precursor to the mature form. In the present study, we compared the precursor and mature forms of recombinant human IL-1α, IL-1β, and IL-33 proteins on the induction of cytokines from A549 cells as well as from human peripheral blood mononuclear cells (PBMC). Similar to the mature form, the IL-1α precursor was active in inducing IL-6 and TNFα, whereas the precursor forms of IL-1β and IL-33 were not active. On PBMC, precursor and mature IL-1α at 0.04 and 0.2 nM were equally active in inducing IL-6. Given the fact that during necrotic cell death, the IL-1α precursor is released intact and triggers IL-1 receptors on tissue macrophages, these data identify the precursor form of IL-1α as a key player in sterile inflammation. |
| Related Links | http://dx.doi.org/10.3389/fimmu.2013.00391 |
| Starting Page | 391 |
| File Format | |
| ISSN | 16643224 |
| e-ISSN | 16643224 |
| Journal | Frontiers in Immunology |
| Volume Number | 4 |
| Language | English |
| Publisher | Frontiers Media S.A. |
| Publisher Date | 2013-11-20 |
| Access Restriction | Open |
| Rights Holder | Frontiers Media S.A. |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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