ArticleThe Journal of biological chemistry2013
Toll-like receptor agonists and febrile range hyperthermia synergize to induce heat shock protein 70 expression and extracellular release.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- A systematic review of protein post-translational modifications in sepsis.Molecular biology reports · 2025Pooled it
- Thermal modulation enhances antitumour immunity and improves immunotherapy responses in lung cancer.Discover oncology · 2026Review
- Monophosphoryl lipid A as a co-adjuvant in methicillin-resistant Staphylococcus aureus vaccine development: improvement of immune responses in a mouse model of infection.Immunologic research · 2024Article
- Fever-Range Hyperthermia Promotes Macrophage Polarization towards Regulatory Phenotype M2b.International journal of molecular sciences · 2023Article
- Role of heat shock protein 70 in regulation of anti-inflammatory response to curcumin in 3T3-L1 adipocytes.Nutrition research and practice · 2023Article
- Specific TLR-mediated HSP70 activation plays a potential role in host defense against the intestinal parasiteFrontiers in microbiology · 2023Article
- Drug-Induced Hyperthermia Review.Cureus · 2022Review
- Laser ablation: Heating up the anti-tumor response in the intracranial compartment.Advanced drug delivery reviews · 2022Review
- NKT-like (CD3 + CD56+) cells differ from T cells in expression level of cellular protective proteins and sensitivity to stimulation in the process of ageing.Immunity & ageing : I & A · 2022Article
- The Correlation between Extracellular Heat Shock Protein 70 and Lipid Metabolism in a Ruminant Model.Metabolites · 2021Article
- Extracellular Vesicles: A Double-Edged Sword in Sepsis.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Short communication: preliminary observations on the serum levels of HSP70 and its correlation with serum cortisol, thyroid hormones, and acute-phase protein concentration in cattle naturally infected with foot-and-mouth disease virus.Tropical animal health and production · 2021Article
- The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response.Archives of toxicology · 2021Review
- Increased Levels of Plasma Extracellular Heat-Shock Proteins 60 and 70 kDa Characterized Early-Onset Neonatal Sepsis.Frontiers in pediatrics · 2021Article
- Effects of Initial Periodontal Therapy on Heat Shock Protein 70 Levels in Gingival Crevicular Fluid from Periodontitis Patients.Journal of clinical medicine · 2020Article
- Monophosphoryl-Lipid A (MPLA) is an Efficacious Adjuvant for Inactivated Rabies Vaccines.Viruses · 2019Article
- A temperature-dependent conformational shift in p38α MAPK substrate-binding region associated with changes in substrate phosphorylation profile.The Journal of biological chemistry · 2019Article
- Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation.Nutrients · 2018Review
- A role for heat shock factor 1 in hypercapnia-induced inhibition of inflammatory cytokine expression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Extracellular Hsp70 induces inflammation and modulates LPS/LTA-stimulated inflammatory response in THP-1 cells.Cell stress & chaperones · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Heat shock protein (Hsp) 70 expression can be stimulated by febrile range temperature (FRT). Hsp70 has been shown to be elevated in serum of patients with sepsis, and when released from cells, extracellular Hsp70 exerts endotoxin-like effects through Toll-like receptor 4 (TLR4) receptors. Circulating TLR agonists and fever both persist for the first several days of sepsis, and each can activate Hsp70 expression; however, the effect of combined exposure to FRT and TLR agonists on Hsp70 expression is unknown. We found that concurrent exposure to FRT (39.5 °C) and agonists for TLR4 (LPS), TLR2 (Pam3Cys), or TLR3 (poly(IC)) synergized to increase Hsp70 expression and extracellular release in RAW264.7 macrophages. The increase in Hsp70 expression was associated with activation of p38 and ERK MAP kinases, phosphorylation of histone H3, and increased recruitment of HSF1 to the Hsp70 promoter. Pretreatment with the p38 MAPK inhibitor SB283580 but not the ERK pathway inhibitor UO126 significantly reduced Hsp70 gene modification and Hsp70 expression in RAW cells co-exposed to LPS and FRT. In mice challenged with intratracheal LPS and then exposed to febrile range hyperthermia (core temperature, ∼39.5 °C), Hsp70 levels in lung tissue and in cell-free lung lavage were increased compared with mice exposed to either hyperthermia or LPS alone. We propose a model of how enhanced Hsp70 expression and extracellular release in patients concurrently exposed to fever and TLR agonists may contribute to the pathogenesis of sepsis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.