The small heat shock protein HSPB1 protects mice from sepsis

Breed, Elise R.; Hilliard, Carolyn A.; Yoseph, Benyam P.; Mittal, Rohit; Liang, Zhe; Chen, Ching-Wen; Burd, Eileen M.; Brewster, Luke P.; Hansen, Laura; Gleason, Rudolph L.; Pandita, Tej K.; Ford, Mandy L.; Hunt, Clayton R.; Coopersmith, Craig M.

doi:10.1038/s41598-018-30752-8

Cited by 11 publications

(10 citation statements)

References 56 publications

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“…An earlier report using HeLa cells showed that HSPB1 is associated with the expression of proinflammatory factors and involved in the IL-1 and TNFinduced signaling [72]. In C6 glioma cells, the chaperone activity of HSPB1 contributed to the production of the pro-inflammatory cytokine, IL-6, whereas T cells from HSPB1 −/− mice exhibited reduced secretion of TNF and IL-2 [74,75]. Recombinant HSPB1 treatment also resulted in enhanced pro-inflammatory cytokine expression in vitro [18,76,77].…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammatory processes are augmented in mice overexpressing human heat-shock protein B1 following ethanol-induced brain injury

Dukay

Walter

Vigh

et al. 2021

J Neuroinflammation

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Background Heat-shock protein B1 (HSPB1) is among the most well-known and versatile member of the evolutionarily conserved family of small heat-shock proteins. It has been implicated to serve a neuroprotective role against various neurological disorders via its modulatory activity on inflammation, yet its exact role in neuroinflammation is poorly understood. In order to shed light on the exact mechanism of inflammation modulation by HSPB1, we investigated the effect of HSPB1 on neuroinflammatory processes in an in vivo and in vitro model of acute brain injury. Methods In this study, we used a transgenic mouse strain overexpressing the human HSPB1 protein. In the in vivo experiments, 7-day-old transgenic and wild-type mice were treated with ethanol. Apoptotic cells were detected using TUNEL assay. The mRNA and protein levels of cytokines and glial cell markers were examined using RT-PCR and immunohistochemistry in the brain. We also established primary neuronal, astrocyte, and microglial cultures which were subjected to cytokine and ethanol treatments. TNFα and hHSPB1 levels were measured from the supernates by ELISA, and intracellular hHSPB1 expression was analyzed using fluorescent immunohistochemistry. Results Following ethanol treatment, the brains of hHSPB1-overexpressing mice showed a significantly higher mRNA level of pro-inflammatory cytokines (Tnf, Il1b), microglia (Cd68, Arg1), and astrocyte (Gfap) markers compared to wild-type brains. Microglial activation, and 1 week later, reactive astrogliosis was higher in certain brain areas of ethanol-treated transgenic mice compared to those of wild-types. Despite the remarkably high expression of pro-apoptotic Tnf, hHSPB1-overexpressing mice did not exhibit higher level of apoptosis. Our data suggest that intracellular hHSPB1, showing the highest level in primary astrocytes, was responsible for the inflammation-regulating effects. Microglia cells were the main source of TNFα in our model. Microglia isolated from hHSPB1-overexpressing mice showed a significantly higher release of TNFα compared to wild-type cells under inflammatory conditions. Conclusions Our work provides novel in vivo evidence that hHSPB1 overexpression has a regulating effect on acute neuroinflammation by intensifying the expression of pro-inflammatory cytokines and enhancing glial cell activation, but not increasing neuronal apoptosis. These results suggest that hHSPB1 may play a complex role in the modulation of the ethanol-induced neuroinflammatory response.

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Section: Discussionmentioning

confidence: 99%

Neuroinflammatory processes are augmented in mice overexpressing human heat-shock protein B1 following ethanol-induced brain injury

Dukay

Walter

Vigh

et al. 2021

J Neuroinflammation

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“…This limited protection could be explained by the contribution of different factors, including other isoforms of Hsp70, Hsp40, Hsp27, and Hsp90, which share overlapping function at different levels. In addition to the induction of atopic dermatitis, Hsp27 is known to contribute in the production of proinflammatory cytokines (19,32,33). Pezzulo et al (34) have demonstrated the critical role of Hsp90 in the induction of goblet cell hyperplasia and mucus production.…”

Section: Hsp70 Induces Th2 Responses and Airway Inflammationmentioning

confidence: 99%

Heat shock protein 70 is a positive regulator of airway inflammation and goblet cell hyperplasia in a mouse model of allergic airway inflammation

Kalenda

Mentink‐Kane

Wilson

et al. 2019

Journal of Biological Chemistry

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Heat shock proteins (Hsps) are highly conserved molecular chaperones that are ubiquitously expressed in all species to aid the solubilization of misfolded proteins, protein degradation, and transport. Elevated levels of Hsp70 have been found in the sputum, serum, and bronchoalveolar lavage (BAL) fluid of asthma patients and are known to correlate with disease severity. However, the function of Hsp70 in allergic airway inflammation has remained largely unknown. This study aimed to determine the role of Hsp70 in airway inflammation and remodeling using a mouse model of allergic airway inflammation. WT and Hsp70 double-knockout (Hsp70.1/.3 ؊/؊) mice were sensitized and challenged intratracheally with Schistosoma mansoni soluble egg antigens (SEAs) to induce robust Th2 responses and airway inflammation in the lungs. The lack of Hsp70 resulted in a significant reduction in airway inflammation, goblet cell hyperplasia, and Th2 cytokine production, including IL-4, IL-5, and IL-13. An analysis of the BAL fluid suggested that Hsp70 is critically required for eosinophilic infiltration, collagen accumulation, and Th2 cytokine production in allergic airways. Furthermore, our bone marrow (BM) transfer studies show that SEA-induced airway inflammation, goblet cell hyperplasia, and Th2 cytokine production were attenuated in WT mice that were reconstituted with Hsp70-deficient BM, but these effects were not attenuated in Hsp70-deficient mice that were reconstituted with WT BM. Together, these studies identify a pathogenic role for Hsp70 in hematopoietic cells during allergic airway inflammation; this illustrates the potential utility of targeting Hsp70 to alleviate allergen-induced Th2 cytokines, goblet cell hyperplasia, and airway inflammation.

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“…The HSPB1 gene expresses HSPB1, heat shock protein beta-1 protein (also known as Hsp27, heat shock protein 27). This protein is a member of the heat shock protein family, which helps to protect cells under adverse conditions such as infection, inflammation, exposure to toxins, elevated temperature, injury, and disease [19]. HSPB1 acts as a potent inhibitor of apoptosis signaling [20].…”

Section: Resultsmentioning

confidence: 99%

Apoptosis and Cell Cycle Pathway-Focused Genes Expression Analysis in Patients with Different Forms of Thyroid Pathology

Bilous¹,

Pavlovych²,

Krynytska³

et al. 2020

Open Access Maced J Med Sci

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BACKGROUND: Thyroid hormones are key regulators of essential cellular processes including proliferation, differentiation, and finally apoptosis. AIM: The aim of study was to detect changes in the expression of apoptosis and cell cycle pathway-focused genes in patients with different forms of thyroid pathology. PATIENTS AND METHODS: 36 patients with thyroid pathology were enrolled in the study. We used the pathway-specific real-time PCR array (Neurotrophins and Receptors RT2 Profiler PCR Array, QIAGEN, Germany) to identify and verify apoptosis and cell cycle pathway-focused genes expression in patients with postoperative hypothyroidism, hypothyroidism as a result of autoimmune thyroiditis (AIT) and AIT with elevated serum an anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies. RESULTS: It was shown that patients with elevated serum anti-Tg and anti-TPO antibodies and with hypothyroidism resulting from AIT had a significantly lower expression of FAS, TGFB, TP53, TGFA, while the expression of CD40 was increased. The mRNA levels of BCL2 and BAX decreased in the patients with elevated serum anti-Tg and anti-TPO antibodies and increased in the patients with hypothyroidism resulting from AIT and postoperative hypothyroidism. The patients with hypothyroidism resulting from AIT and postoperative hypothyroidism had significantly lower expression of HSPB1. NF1 expression did not change in all groups of patients. CONCLUSION: The results of this study demonstrate that AIT and hypothyroidism affect the mRNA-level expression of apoptosis and cell cycle pathway-focused genes in gene specific manner and that these changes to gene expression can be responsible for the apoptosis signs and symptoms associated with thyroid pathology.

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The small heat shock protein HSPB1 protects mice from sepsis

Cited by 11 publications

References 56 publications

Neuroinflammatory processes are augmented in mice overexpressing human heat-shock protein B1 following ethanol-induced brain injury

Neuroinflammatory processes are augmented in mice overexpressing human heat-shock protein B1 following ethanol-induced brain injury

Heat shock protein 70 is a positive regulator of airway inflammation and goblet cell hyperplasia in a mouse model of allergic airway inflammation

Apoptosis and Cell Cycle Pathway-Focused Genes Expression Analysis in Patients with Different Forms of Thyroid Pathology

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