Heat shock proteins 27 and 70 regulating angiotensin II-induced NF-κB: a possible connection to blood pressure control?

Voegeli, Tracy S.; Wintink, Amanda J.; Chen, Yu; Currie, R. William

doi:10.1139/h08-068

Cited by 19 publications

(13 citation statements)

References 63 publications

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“…Accumulating evidence suggests that the protective (antiinflammatory) role of Hsp70 is mediated through downregulation of NF-κB, since NF-κB activation and translocation into the nucleus promotes elevated proinflammatory mediators (14,(16)(17)(18)(19)(20)(21)41,50,72,73). Consistent with this notion, we and others have demonstrated that overexpression of Hsp70 protein blocks nuclear translocation of NF-κB and thereby reduces proinflammatory mediator production (19)(20)(21)50).…”

Section: Discussionsupporting

confidence: 75%

“…Since circulating levels of Gln were significantly reduced in children with SMA (see Figure 5A), and Gln improves clinical outcomes in acute illness and injury through increasing Hsp70 expression, an event that attenuates NF-κB translocation to nucleus (28,41,54), we determined whether the addition of Gln could overcome PfHz-induced against severe disease. Since our studies are conducted in a holoendemic P. falciparum transmission region of western Kenya, nearly all the children get repeated episodes of malaria prior to developing naturally acquired immunity.…”

Section: Effect Of Glutamine On Hemozoininduced Suppression Of Hsp70mentioning

confidence: 99%

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Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

Kempaiah

Dokładny

Karim

et al. 2016

Mol Med

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Severe malarial anemia (SMA; hemoglobin [Hb] <5.0 g/dL) is a leading global cause of morbidity and mortality among children residing in Plasmodium falciparum transmission regions. Exploration of molecular pathways through global gene expression profiling revealed that SMA was characterized by decreased HSPA1A, a heat shock protein 70 (Hsp70) coding gene. Hsp70 is a ubiquitous chaperone that regulates nuclear factor-kappa B (NF-κB) signaling and production of proinflammatory cytokines known to be important in malaria pathogenesis (for example, IL-1β, IL-6 and TNF-α). Since the role of host Hsp70 in malaria pathogenesis is unexplored, we investigated Hsp70 and molecular pathways in children with SMA. Validation experiments revealed that leukocytic HSP70 transcripts were reduced in SMA relative to nonsevere malaria, and that intraleukocytic hemozoin (PfHz) was associated with lower HSP70. HSP70 was correlated with reticulocyte production and Hb. Since glutamine (Gln) upregulates Hsp70, modulates NF-κB activation and attenuates overexpression of proinflammatory cytokines, circulating Gln was measured in children with malaria. Reduced Gln was associated with increased risk of developing SMA. Treatment of cultured peripheral blood mononuclear cells (PBMCs) with PfHz caused a time-dependent decrease in Hsp70 transcripts/protein and NF-κB activation. Gln treatment of PBMCs overcame PfHz-induced suppression of HSP70 transcripts/protein, reduced NF-κB activation and suppressed overexpression of IL-1β, IL-6 and TNF-α. These findings demonstrate that SMA is characterized by reduced intraleukocytic HSP70 and circulating Gln, and that PfHz-induced suppression of HSP70 can be reversed by Gln. Thus, Gln supplementation may offer important immunotherapeutic options for futures studies in children with SMA.

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Section: Discussionsupporting

confidence: 75%

Section: Effect Of Glutamine On Hemozoininduced Suppression Of Hsp70mentioning

confidence: 99%

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

Kempaiah

Dokładny

Karim

et al. 2016

Mol Med

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“…Interestingly, Hsp70 is involved in the regulation of Ang IIinduced NF-κB. In agreement, HSPs were related to the proinflammatory transcription factor NF-κB (Voegeli et al 2008).…”

Section: Effect Of Hsp70 On Pro-inflammatory Activation Of Epithelialmentioning

confidence: 56%

Mediators and mechanisms of heat shock protein 70 based cytoprotection in obstructive nephropathy

Mazzei

Docherty

Manucha

2015

Cell Stress and Chaperones

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Urinary heat shock protein 70 (Hsp70) is rapidly increased in patients with clinical acute kidney injury, indicating that it constitutes a component of the endogenous stress response to renal injury. Moreover, experimental models have demonstrated that Hsp70 activation is associated with the cytoprotective actions of several drugs following obstruction, including nitric oxide (NO) donors, geranylgeranylacetone, vitamin D, and rosuvastatin. Discrete and synergistic effects of the biological activities of Hsp70 may explain its cytoprotective role in obstructive nephropathy. Basic studies point to a combination of effects including inhibition of apoptosis and inflammation, repair of damaged proteins, prevention of unfolded protein aggregation, targeting of damaged protein for degradation, and cytoskeletal stabilization as primary effectors of Hsp70 action. This review summarizes our understanding of how the biological actions of Hsp70 may affect renal cytoprotection in the context of obstructive injury. The potential of Hsp70 to be of central importance to the mechanism of action of various drugs that modify the genesis of experimental obstructive nephropathy is considered.

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“…However, despite the substantial evidence that extracelluar HSP27 can act as an anti-inflammatory, the role of extracellular HSP27 in the regulation of NF-κB signaling is unclear. Several studies have examined the affect of intracellular HSP27 on NF-κB; however, these indeterminate results are mainly in cell types that have not been demonstrated to secrete HSP27, such as smooth muscle cells (Parcellier et al 2003;Voegeli et al 2008). Therefore, in the current study, we sought to examine whether extracellular HSP27 could modulate NF-κB signaling in macrophages.…”

Section: Samira Salari and Tara Seibert Contributed Equally To This Workmentioning

confidence: 99%

Extracellular HSP27 acts as a signaling molecule to activate NF-κB in macrophages

Salari

Seibert

Chen

et al. 2013

Cell Stress and Chaperones

114

134

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Heat shock protein 27 (HSP27) shows attenuated expression in human coronary arteries as the extent of atherosclerosis progresses. In mice, overexpression of HSP27 reduces atherogenesis, yet the precise mechanism (s) are incompletely understood. Inflammation plays a central role in atherogenesis, and of particular interest is the balance of pro-and anti-inflammatory factors produced by macrophages. As nuclear factor-kappa B (NF-κB) is a key immune signaling modulator in atherogenesis, and macrophages are known to secrete HSP27, we sought to determine if recombinant HSP27 (rHSP27) alters NF-κB signaling in macrophages. Treatment of THP-1 macrophages with rHSP27 resulted in the degradation of an inhibitor of NF-κB, IκBα, nuclear translocation of the NF-κB p65 subunit, and increased NF-κB transcriptional activity. Treatment of THP-1 macrophages with rHSP27 yielded increased expression of a variety of genes, including the pro-inflammatory factors, IL-1β, and TNF-α. However, rHSP27 also increased the expression of the anti-inflammatory factors IL-10 and GM-CSF both at the mRNA and protein levels. Our study suggests that in macrophages, activation of NF-κB signaling by rHSP27 is associated with upregulated expression and secretion of key pro-and anti-inflammatory cytokines. Moreover, we surmise that it is the balance in expression of these mediators and antagonists of inflammation, and hence atherogenesis, that yields a favorable net effect of HSP27 on the vessel wall.

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Heat shock proteins 27 and 70 regulating angiotensin II-induced NF-κB: a possible connection to blood pressure control?

Cited by 19 publications

References 63 publications

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

Mediators and mechanisms of heat shock protein 70 based cytoprotection in obstructive nephropathy

Extracellular HSP27 acts as a signaling molecule to activate NF-κB in macrophages

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