Activation of hepatocytes by extracellular heat shock protein 72

Galloway, Elizabeth; Shin, Taehoon; Huber, Nadine; Eismann, Thorsten; Kuboki, Satoshi; Schuster, Rebecca; Blanchard, John; Wong, Hector R.; Lentsch, Alex B.

doi:10.1152/ajpcell.00032.2008

Cited by 53 publications

(47 citation statements)

References 41 publications

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“…First of all, it is the time; HSPs induction before a proinflammatory stimulus is clearly beneficial; however, HSPs induction after a pro-inflammatory stimulus is cytotoxic. The second factor is place and sources; HSPs from extracellular or intracellular and different microorganisms may have different role (Galloway et al 2008;Chen et al 2007;Rha et al 2002). Nevertheless, our results definitely support HSP70 as a new biomarker for evaluating the degree of airway obstruction in asthma; however, the source of HSPs in healthy individuals, as well as in patients with pathological conditions, and its exact mechanisms in allergic asthma have not been completely determined yet.…”

Section: Discussionmentioning

confidence: 56%

Increased heat shock protein 70 levels in induced sputum and plasma correlate with severity of asthma patients

Hou

Zhao

et al. 2011

Cell Stress and Chaperones

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Damage-associated molecular pattern molecules such as high-mobility group box 1 protein (HMGB1) and heat shock protein 70 (HSP70) have been implicated in the pathogenesis of asthma. The aim of our study was to examine the induced sputum and plasma concentrations of HSP70 in asthmatic patients to determine their relationship with airway obstruction. Thirty-four healthy controls and 56 patients with persistent bronchial asthma matched for gender and age were enrolled in this study. Spirometry measurements were performed before sputum induction. HSP70 levels in induced sputum and plasma were measured using the ELISA Kit. Sputum and plasma concentrations of HSP70 in asthmatics patients were significantly higher than that in control subjects (sputum, (0.88 ng/ml (0.27-1.88 ng/ml) versus 0.42 ng/ml (0.18-0.85 ng/ml), p < 0.001); plasma, (0.46 ng/ml (0.20-0.98 ng/ml) versus 0.14 ng/ml (0.11-0.37 ng/ml), p<0.001) and were significantly negatively correlated with forced expiratory volume in 1 s (FEV1), FEV1 (percent predicted), and FEV1/FVC in all 90 participants and 56 patients with asthma. There were no significant differences in HSP70 levels between patients with eosinophilic and noneosinophilic asthma. HSP70 levels in plasma were positively correlated with neutrophil count, and HSP70 levels in induced sputum were positively correlated with lymphocyte count. In multivariate analysis, independent predictors of sputum HSP70 were diseases and disease severity but not smoking, age, or gender, and independent predictors of plasma HSP70 were also diseases and disease severity. In conclusion, this study indicates that induced sputum and plasma HSP70 could serve as a useful marker for assessing the degree of airway obstruction in patients with asthma. However, further investigation is needed to establish the role of circulating and sputum HSP70 in the pathogenesis of asthma.

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Section: Discussionmentioning

confidence: 56%

Increased heat shock protein 70 levels in induced sputum and plasma correlate with severity of asthma patients

Hou

Zhao

et al. 2011

Cell Stress and Chaperones

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“…Correspondingly, microvascular complications induced by the activation of PKC-β in target organs, such as increased glomerular filtration rate and retinal edema, could be diminished by treatment with the PKC-β inhibitor Rx (17). The activation and expression of NF-κB plays a specific role in the development of I/R injury in the heart, brain, liver, kidney and other organs, which is described as cyclic activation (18,19). NF-κB regulates the genetic expression of ICAM-1 of the adhesion molecule family, the proinflammatory factor TNF-α and P-selectin.…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C-β inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats

Meng

Yuan

Wei

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Hepatic ischemia and reperfusion (I/R) injury plays an active role in hepatic resection and transplantation. While the effects of protein kinase C (PKC)-βII activation and the role of PKC-β inhibitors are well understood in myocardial I/R in diabetes, they remain unclear in liver I/R. The aim of this study was to explore the effect of PKC-β inhibition and the potential mechanism by which PKC-β inhibitor treatment protects against hepatic I/R injury in diabetic rats. Diabetic rats were established and randomized into two groups. These were an untreated group (n=10), which did not receive any treatment, and a treatment group (n=10), orally treated with ruboxistaurin at a dose of 5 mg/kg/day for 2 weeks. The rats from the two groups were subjected to hepatic I/R. Aspartate transaminase (AST) and lactate dehydrogenase (LDH) levels were measured by enzymatic methods at 1, 3 and 5 h after I/R. Tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule 1 (ICAM-1) were examined by enzyme-linked immunosorbent assay at the same time-points. Nuclear factor-κB (NF-κB) p65 expression was analyzed by immunofluorescence and western blotting. Apoptosis of hepatic cells was examined by the western blot analysis of caspase 3 expression and by DNA ladder analysis. Pathological changes were examined using light and electron microscopy. Serum AST and LDH levels in the PKC-β inhibitor treatment group were diminished compared with those in the untreated group (P<0.01). Serum TNF-α and ICAM-1 (P<0.01) levels were also decreased at different time-points in the PKC-β inhibitor treatment group. The relative expression of NF-κB p65 and caspase 3 in the hepatic tissue was weakened in the PKC-β inhibitor treatment group compared with that in the untreated group (P<0.01). Pathological changes in hepatic tissue were attenuated by the PKC-β inhibitor. In conclusion, PKC-β inhibitor treatment protected against liver I/R injury in diabetic rats. The mechanisms probably involved the attenuation of microvascular injury, reduced transport of injury-associated factors and diminishment of the activation of NF-κB p65.

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“…20,39). More recently, extracellular inducible hsp70 has been reported to increase activation of hepatocytes following ischemia-reperfusion injury (40) and to induce airway inflammatory responses (41). Importantly, extracellular hsc70 was shown to play a critical role in myocardial inflammation following injury (42).…”

Section: Discussionmentioning

confidence: 99%

“…Primers used for hsc70 genotyping and RT-PCR were H1 (3Ј-tggcttagacaaaaaggttgg), and H2 (3Ј-cttggggatacgggttgag) and control ␤-actin primers were Act1 (3Ј-atggatgacgatatcgctgc) and Act2 (3Ј-ctagaagcacttgcggtgcac). Peptide gp [33][34][35][36][37][38][39][40][41] …”

Section: Chemicals and Reagentsmentioning

confidence: 99%

“…RIP-GP/P14 TCR mice can be stimulated to acquire diabetes using antigenic peptide plus a strong innate activation signal, such as LPS, anti-CD40, CpG ODN, or hsp70 (22,28,29). To ensure P14 T cells were not tolerant to glycoprotein in the RIP-HSC70 background, we administered peptide gp [33][34][35][36][37][38][39][40][41] plus LPS to triple Tg mice and assessed the ability to stimulate APC and T cell activation. The presence of hsc70 in ␤ cells had no effect on the ability of peptide immunization to activate diabetogenic P14 T cell function, leading to destruction of ␤ cells and hyperglycemia (Fig.…”

Section: Characterization Of Rip-hsc70 Tg Micementioning

confidence: 99%

See 1 more Smart Citation

Transgenic Expression of Hsc70 in Pancreatic Islets Enhances Autoimmune Diabetes in Response to β Cell Damage

Alam

Harken

Knorn

et al. 2009

The Journal of Immunology

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Inflammation following tissue damage promotes lymphocyte recruitment, tissue remodelling, and wound healing while maintaining self tolerance. Endogenous signals associated with tissue damage and cell death have been proposed to initiate and instruct immune responses following injury. Here we have examined the effects of elevated levels of a candidate endogenous danger signal, heat shock cognate protein 70 (Hsc70), on stimulation of inflammation and autoimmunity following cell damage. We find that damage to pancreatic β-cells expressing additional cytosolic Hsc70 leads to an increased incidence of diabetes in a transgenic mouse model. Steady-state levels of activated APC and T cell populations in the draining lymph node were enhanced, which further increased following streptozotocin-induced β-cell death. In addition, pro-inflammatory serum cytokines, and lymphocyte recruitment were increased in Hsc70 transgenic mice. Islet-antigen-specific T cells underwent a greater extent of proliferation in the lymph nodes of mice expressing Hsc70 following β-cell damage, suggesting elevated antigen presentation following release of antigen in the presence of Hsc70. These findings suggest that an elevated content of Hsc70 in cells undergoing necrotic or apoptotic cell death can increase the extent of sterile inflammation and increase the susceptibility to autoimmunity.

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Activation of hepatocytes by extracellular heat shock protein 72

Cited by 53 publications

References 41 publications

Increased heat shock protein 70 levels in induced sputum and plasma correlate with severity of asthma patients

Increased heat shock protein 70 levels in induced sputum and plasma correlate with severity of asthma patients

Protein kinase C-β inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats

Transgenic Expression of Hsc70 in Pancreatic Islets Enhances Autoimmune Diabetes in Response to β Cell Damage

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