Heat shock proteins HSP70 and HSP27 in the cerebral spinal fluid of patients undergoing thoracic aneurysm repair correlate with the probability of postoperative paralysis

Veterinary Immunology and Immunopathology

Maiolini

et al. 2012

The role of extracellular 70 kDa heat shock protein 70 (ehsp70) in central nervous system inflammation is vastly understudied, despite evidence supporting the ability to drive a pro-inflammatory state. We investigated the presence of ehsp70 in cerebrospinal fluid (CSF) and serum of dogs with Steroid Responsive Meningitis-Arteritis (SRMA), with the hypothesis that an ehsp70 response would occur, and might play a role in the pathogenesis of this disease. Samples from 30 dogs acutely affected with SRMA, and 30 dogs treated with corticosteroids and currently in clinical remission from SRMA were compared with normal dogs. Serum and CSF concentrations of ehsp70 were quantified using an enzyme-linked immunosorbent assay. An ehsp70 response occurred in the CSF of dogs with SRMA and this response was attenuated by corticosteroid treatment. There was no correlation between serum and CSF concentrations of ehsp70, supporting local production and release of ehsp70 and not simply leakage from serum. Dogs with SRMA thus represent a powerful spontaneous model by which to study the role of ehsp70 in CNS inflammation.

Section: Introductionmentioning

confidence: 99%

Extracellular hsp70 release in Canine Steroid Responsive Meningitis-Arteritis

Moore

Veterinary Immunology and Immunopathology

Maiolini

et al. 2012

“…Therefore, in the realm of neuroprotection, Hsp70 might be a useful target molecule for the therapeutic treatment. Previous studies have demonstrated that the induction of Hsp70 may be responsible for secondary processes after SCI [38,39]. Recent experimental evidence showed that upregulation of Hsp 70 with pharmacological inhibition of inflammation achieved a neuroprotective effect [31,32].…”

Section: Discussionmentioning

confidence: 99%

Loss ofhsp70.1Decreases Functional Motor Recovery after Spinal Cord Injury in Mice

Jung

Korean J Physiol Pharmacol

et al. 2010

Heat shock proteins (HSPs) are specifically induced by various forms of stress. Hsp70.1, a member of the hsp70 family is known to play an important role in cytoprotection from stressful insults. However, the functional role of Hsp70 in motor function after spinal cord injury (SCI) is still unclear. To study the role of hsp70.1 in motor recovery following SCI, we assessed locomotor function in hsp70.1 knockout (KO) mice and their wild-type (W T) mice via the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, before and after spinal hemisection at T13 level. W e also examined lesion size in the spinal cord using Luxol fast blue/cresyl violet staining. One day after injury, KO and W T mice showed no significant difference in the motor function due to complete paralysis following spinal hemisection. However, when it compared to W T mice, KO mice had significantly delayed and decreased functional outcomes from 4 days up to 21 days after SCI. KO mice also showed significantly greater lesion size in the spinal cord than WT mice showed at 21 days after spinal hemisection. These results suggest that Hsp70 has a protective effect against traumatic SCI and the manipulation of the hsp70.1 gene may help improve the recovery of motor function, thereby enhancing neuroprotection after SCI.

“…Release of hsp70 into cerebrospinal fluid (CSF) of the central nervous system (CNS) is an emerging field of research. Increased hsp70 levels in CSF have been reported in association with the inflammatory response to ischemia-reperfusion injury in spinal cords of humans and dogs [92,93]. Data from the ischemic-reperfusion injury model in dogs supports secretory release from within the CNS since hsp70 levels in serum was unaffected [92].…”

Section: Extracellular Hsp70mentioning

confidence: 99%

Virus-Heat Shock Protein Interaction and a Novel Axis for Innate Antiviral Immunity

Oglesbee

2012

Cells

Virus infections induce heat shock proteins that in turn enhance virus gene expression, a phenomenon that is particularly well characterized for the major inducible 70 kDa heat shock protein (hsp70). However, hsp70 is also readily induced by fever, a phylogenetically conserved response to microbial infections, and when released from cells, hsp70 can stimulate innate immune responses through toll like receptors 2 and 4 (TLR2 and 4). This review examines how the virus-hsp70 relationship can lead to host protective innate antiviral immunity, and the importance of hsp70 dependent stimulation of virus gene expression in this host response. Beginning with the well-characterized measles virus-hsp70 relationship and the mouse model of neuronal infection in brain, we examine data indicating that the innate immune response is not driven by intracellular sensors of pathogen associated molecular patterns, but rather by extracellular ligands signaling through TLR2 and 4. Specifically, we address the relationship between virus gene expression, extracellular release of hsp70 (as a damage associated molecular pattern), and hsp70-mediated induction of antigen presentation and type 1 interferons in uninfected macrophages as a novel axis of antiviral immunity. New data are discussed that examines the more broad relevance of this protective mechanism using vesicular stomatitis virus, and a review of the literature is presented that supports the probable relevance to both RNA and DNA viruses and for infections both within and outside of the central nervous system.