Asea, Alexzander and Rehli, Michael and Kabingu, Edith and Boch, Jason A. and Bare, Olivia and Auron, Philip E. and Stevenson, Mary Ann and Calderwood, Stuart K. (2002) Novel signal transduction pathway utilized by extracellular HSP70 - Role of Toll-like receptor (TLR) 2 AND TLR4. JOURNAL OF BIOLOGICAL CHEMISTRY, 277 (17). pp. 15028-15034. ISSN 0021-9258
Full text not available from this repository. (Request a copy)Abstract
Recent studies have initiated a paradigm shift in the understanding of the function of heat shock proteins (HSP). It is now clear that HSP can and do exit mammalian cells, interact with cells of the immune system, and exert immunoregulatory effects. We recently demonstrated that exogenously added HSP70 possesses potent cytokine activity, with the ability to bind with high affinity to the plasma membrane, elicit a rapid intracellular Ca2+ flux, activate NF-kappaB, and up-regulate the expression of pro-inflammatory cytokines in human monocytes. Here for the first time, we report that HSP70-induced proinflammatory cytokine production is mediated via the MyD88/IRAK/NF-kappaB signal transduction pathway and that HSP70 utilizes both TLR2 (receptor for Gram-positive bacteria) and TLR4 (receptor for Gram-negative bacteria) to transduce its proinflammatory signal in a CD14-dependent fashion. These studies now pave the way for the development of highly effective pharmacological or molecular tools that will either up-regulate or suppress HSP70-induced functions in conditions where HSP70 effects are desirable (cancer) or disorders where HSP70 effects are undesirable (arthritis and arteriosclerosis).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INNATE IMMUNE-RESPONSE; HEAT-SHOCK PROTEINS; BINDING PROTEINS; DROSOPHILA TOLL; FAMILY; MYD88; CELLS; ENDOTOXIN; MICE; HEAT-SHOCK-PROTEIN-70; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Nov 2021 07:18 |
| Last Modified: | 02 Nov 2021 07:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40375 |
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