Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4
- PMID: 11836257
- DOI: 10.1074/jbc.M200497200
Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4
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 Ca(2+) 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).
Similar articles
-
Heat shock up-regulates expression of Toll-like receptor-2 and Toll-like receptor-4 in human monocytes via p38 kinase signal pathway.Immunology. 2005 Apr;114(4):522-30. doi: 10.1111/j.1365-2567.2004.02112.x. Immunology. 2005. PMID: 15804289 Free PMC article.
-
Chaperokine-induced signal transduction pathways.Exerc Immunol Rev. 2003;9:25-33. Exerc Immunol Rev. 2003. PMID: 14686091 Free PMC article. Review.
-
HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway.J Biol Chem. 2002 Apr 26;277(17):15107-12. doi: 10.1074/jbc.M111204200. Epub 2002 Feb 12. J Biol Chem. 2002. PMID: 11842086
-
Toll-like receptors; their physiological role and signal transduction system.Int Immunopharmacol. 2001 Apr;1(4):625-35. doi: 10.1016/s1567-5769(01)00010-8. Int Immunopharmacol. 2001. PMID: 11357875 Review.
-
Micrococci and peptidoglycan activate TLR2-->MyD88-->IRAK-->TRAF-->NIK-->IKK-->NF-kappaB signal transduction pathway that induces transcription of interleukin-8.Infect Immun. 2001 Apr;69(4):2270-6. doi: 10.1128/IAI.69.4.2270-2276.2001. Infect Immun. 2001. PMID: 11254583 Free PMC article.
Cited by
-
Transcriptional control of metabolism by interferon regulatory factors.Nat Rev Endocrinol. 2024 May 20. doi: 10.1038/s41574-024-00990-0. Online ahead of print. Nat Rev Endocrinol. 2024. PMID: 38769435 Review.
-
Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target.Front Oncol. 2024 Apr 5;14:1388999. doi: 10.3389/fonc.2024.1388999. eCollection 2024. Front Oncol. 2024. PMID: 38646439 Free PMC article. Review.
-
The contribution of pattern recognition receptor signalling in the development of age related macular degeneration: the role of toll-like-receptors and the NLRP3-inflammasome.J Neuroinflammation. 2024 Mar 5;21(1):64. doi: 10.1186/s12974-024-03055-1. J Neuroinflammation. 2024. PMID: 38443987 Free PMC article. Review.
-
Deciphering the immunological interactions: targeting preeclampsia with Hydroxychloroquine's biological mechanisms.Front Pharmacol. 2024 Feb 5;15:1298928. doi: 10.3389/fphar.2024.1298928. eCollection 2024. Front Pharmacol. 2024. PMID: 38375029 Free PMC article. Review.
-
Damage-Associated Molecular Patterns, a Class of Potential Psoriasis Drug Targets.Int J Mol Sci. 2024 Jan 7;25(2):771. doi: 10.3390/ijms25020771. Int J Mol Sci. 2024. PMID: 38255845 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous