Heat shock proteins and innate immunity

Gaston, J. S. H.

doi:10.1046/j.1365-2249.2002.01759.x

Cited by 37 publications

(20 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TLR binding leads to NF-kB activation with subsequent upregulation of pro-inflammatory cytokines and iNOS [78]. Hsp60 and Hsp90 have also been shown to interact with TLR2 and TLR4 [79]; however, some of this work has been questioned, since some preparations of recombinant HSPs may contain low levels of endotoxin, which is a classic ligand for TLR4 [80]. …”

Section: Hsp70 In Inflammationmentioning

confidence: 99%

The 70-kDa heat shock protein (Hsp70) as a therapeutic target for stroke

Kim

Han

Lee

et al. 2018

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

Introduction: The 70-kDa heat shock protein (Hsp70) is a cytosolic chaperone which facilitates protein folding, degradation, complex assembly, and translocation. Following stroke, these functions have the potential to lead to cytoprotection, and this has been demonstrated using genetic mutant models, direct gene transfer or the induction of Hsp70 via heat stress, approaches which limit its translational utility. Recently, the investigation of Hsp70-inducing pharmacological compounds, which, through their ability to inhibit Hsp90, has obvious clinical implications in terms of potential therapies to mitigate cell death and inflammation, and lead to neuroprotection from brain injury. Areas covered: In this review, we will focus on the role of Hsp70 in cell death and inflammation, and the current literature surrounding the pharmacological induction in acute ischemic stroke models with comments on potential applications at the clinical level. Expert opinion: Such neuroprotectants could be used to synergistically improve neurological outcome or to extend the time window of existing interventions, thus increasing the numbers of stroke victims eligible for treatment.

show abstract

Section: Hsp70 In Inflammationmentioning

confidence: 99%

The 70-kDa heat shock protein (Hsp70) as a therapeutic target for stroke

Kim

Han

Lee

et al. 2018

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

show abstract

“…They can interact with macrophages, microglia and dendritic cells through Toll-like receptors (TLRs) and lead to NF-kB activation with subsequent upregulation of pro-inflammatory cytokines and iNOS (Giffard et al 2008;Srivastava 2002). Hsp60, Hsp70 and Hsp90 are all thought to interact with TLR 2 and TLR4 (Asea 2008;Asea et al 2002); however, some of this work has been questioned, since some preparations of recombinant Hsps may contain low levels of endotoxin, which is the classic ligand for TLR4 (Gaston 2002).…”

Section: Hsp70 In Inflammationmentioning

confidence: 99%

Anti-inflammatory properties and pharmacological induction of Hsp70 after brain injury

Kim

Yenari

2012

Inflammopharmacol

View full text Add to dashboard Cite

The 70-kDa heat shock protein (Hsp70) is thought to protect the brain from a variety of insults. Although the mechanism has been largely limited to its chaperone functions, recent work indicates that Hsp70 also modulates inflammatory pathways. Brain injury and ischemia are associated with an immune response that is largely innate. Hsp70 appears to suppress this response and lead to improved neurological outcome. However, most of this work has relied on the use of genetic mutant models or Hsp70 overexpression using gene transfer or heat stress, thus limiting its translational utility. A few compounds have been studied by various disciplines which, through their ability to inhibit Hsp90, can cause induction of Hsp70. The investigation of Hsp70-inducing pharmacological compounds has obvious clinical implications in terms of potential therapies to mitigate neuroinflammation and lead to neuroprotection from stroke or traumatic brain injury. This review will focus on the inflammation modulating properties of Hsp70, and the current literature surrounding the pharmacological induction in acute neurological injury models with comments on potential applications at the clinical level.

show abstract

“…Although most studies in this area have attempted to exclude contaminating LPS using inhibitors (e.g., polymyxin B) and measuring LPS (via the limulus assay) these measures may not have completely controlled for LPS contamination as HSP may have acted as a chaperone for LPS and shielded it from inhibition by polymyxin. 40,41 Furthermore, some of the products used in these studies were synthesized in prokaryotic organisms. 40,41 In addition, not all of these studies included LPS-insensitive cells derived from TLR 4 mutant mice.…”

Section: Activation Of Tlrs In Thoracic Organ Transplantationmentioning

confidence: 99%

“…40,41 Furthermore, some of the products used in these studies were synthesized in prokaryotic organisms. 40,41 In addition, not all of these studies included LPS-insensitive cells derived from TLR 4 mutant mice. Thus, although endogenous ligands are likely released by the surgical trauma or organ harvest and transplantation, the importance of these molecules in TLR signaling requires further confirmation.…”

Section: Activation Of Tlrs In Thoracic Organ Transplantationmentioning

confidence: 99%