Heat Shock Factor 1 Represses Transcription of the IL-1β Gene through Physical Interaction with the Nuclear Factor of Interleukin 6

Xie, Ying; Chen, Changmin; Stevenson, Mary Ann; Auron, Philip E.; Calderwood, Stuart K.

doi:10.1074/jbc.m109296200

Cited by 163 publications

(151 citation statements)

References 66 publications

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“…Similarly, recent studies have reported that HSF1 acts as a transcriptional repressor of certain cytokine genes, including TNF-a and IL-1b, to prevent LPS-induced inflammation. 29,43,44 These results support our findings that HSF1 protects cardiomyocytes via transcriptional repression of IGF-IIR expression. Our results demonstrate that ANG II represses HSF1 by two mechanisms: (1) phosphorylation of HSF1 Ser303 to inhibit its transcriptional activity and (2) acetylation of HSF1 Lys80 to suppress its DNA-binding activity.…”

Section: Ser303supporting

confidence: 81%

ANG II promotes IGF-IIR expression and cardiomyocyte apoptosis by inhibiting HSF1 via JNK activation and SIRT1 degradation

Huang

et al. 2014

Cell Death Differ

115

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Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure. Our previous studies found that the activation of insulin-like growth factor receptor II (IGF-IIR) signaling was critical for hypertensive angiotensin II (ANG II)-induced cardiomyocyte apoptosis. However, the detailed mechanism by which ANG II regulates IGF-IIR in heart cells remains elusive. In this study, we found that ANG II activated its downstream kinase JNK to increase IGF-IIR expression through the ANG II receptor angiotensin type 1 receptor. JNK activation subsequently led to sirtuin 1 (SIRT1) degradation via the proteasome, thus preventing SIRT1 from deacetylating heat-shock transcription factor 1 (HSF1). The resulting increase in the acetylation of HSF1 impaired its ability to bind to the IGF-IIR promoter region (nt À 748 to À 585). HSF1 protected cardiomyocytes by acting as a repressor of IGF-IIR gene expression, and ANG II diminished this HSF1-mediated repression through enhanced acetylation, thus activating the IGF-IIR apoptosis pathway. Taken together, these results suggest that HSF1 represses IGF-IIR gene expression to protect cardiomyocytes. ANG II activates JNK to degrade SIRT1, resulting in HSF1 acetylation, which induces IGF-IIR expression and eventually results in cardiac hypertrophy and apoptosis. HSF1 could be a valuable target for developing treatments for cardiac diseases in hypertensive patients. Apoptosis has been implicated in a wide variety of cardiovascular disorders, including myocardial infarction and heart failure, suggesting that activation of apoptotic pathways contributes to cardiomyocyte loss and subsequently cardiac dysfunction. Previous studies reported that several extracellular molecules, such as insulin-like growth factors (IGFs) and angiotensin II (ANG II), are involved in the development of cardiac hypertrophy and apoptosis.

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Section: Ser303supporting

confidence: 81%

ANG II promotes IGF-IIR expression and cardiomyocyte apoptosis by inhibiting HSF1 via JNK activation and SIRT1 degradation

Huang

et al. 2014

Cell Death Differ

115

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“…High levels of calgranulin-S100A8/A9 acted as chemoattractant for leucocytes and as an important regulator of inflammation, whose synthesis is enhanced by IL-17A [39]. The heat shock proteins, HSP-27, HSP-60 and HSP-70, interacted with dendritic cells, monocytes and MSC to induce IL-10 synthesis [42,43]; furthermore, activation of the HSP gene (HSF1) would have repressed transcription of IL-1β in the wound site [44]. In short, we propose that sterile trauma induced a DAMP-driven anti-inflammatory milieu, reinforced by IL-6, IL-9, IL-10, TGF-β and IL-1RA, whose primary function was to suppress activation of tissue damaging inflammatory cascades, while simultaneously facilitating tissue regeneration by inducing the chemokines IL-8/CXCL8, MCP-1/CCL2 and MIP-1α/CCL3.…”

Section: Discussionmentioning

confidence: 99%

Post-traumatic immunosuppression is reversed by anti-coagulated salvaged blood transfusion: deductions from studying immune status after knee arthroplasty

Islam

Whitehouse

Mehendale

et al. 2014

Clinical and Experimental Immunology

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SummaryMajor trauma increases vulnerability to systemic infections due to poorly defined immunosuppressive mechanisms. It confers no evolutionary advantage. Our objective was to develop better biomarkers of post-traumatic immunosuppression (PTI) and to extend our observation that PTI was reversed by anti-coagulated salvaged blood transfusion, in the knowledge that others have shown that non-anti-coagulated (fibrinolysed) salvaged blood was immunosuppressive. A prospective non-randomized cohort study of patients undergoing primary total knee arthroplasty included 25 who received salvaged blood transfusions collected post-operatively into acid-citrate-dextrose anti-coagulant (ASBT cohort), and 18 non-transfused patients (NSBT cohort). Biomarkers of sterile trauma included haematological values, damage-associated molecular patterns (DAMPs), cytokines and chemokines. Salvaged blood was analysed within 1 and 6 h after commencing collection. Biomarkers were expressed as fold-changes over preoperative values. Certain biomarkers of sterile trauma were common to all 43 patients, including supranormal levels of: interleukin (IL)-6, IL-1-receptor-antagonist, IL-8, heat shock protein-70 and calgranulin-S100-A8/9. Other proinflammatory biomarkers which were subnormal in NSBT became supranormal in ASBT patients, including IL-1β, IL-2, IL-17A, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and annexin-A2. Furthermore, ASBT exhibited subnormal levels of anti-inflammatory biomarkers: IL-4, IL-5, IL-10 and IL-13. Salvaged blood analyses revealed sustained high levels of IL-9, IL-10 and certain DAMPs, including calgranulin-S100-A8/9, alpha-defensin and heat shock proteins 27, 60 and 70. Active synthesis during salvaged blood collection yielded increasingly elevated levels of annexin-A2, IL-1β, Il-1-receptor-antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, transforming growth factor (TGF)-β1, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α. Elevated levels of high-mobility group-box protein-1 decreased. In conclusion, we demonstrated that anti-coagulated salvaged blood reversed PTI, and was attributed to immune stimulants generated during salvaged blood collection.

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“…For example, HSF1 binds the 5'-untranslated region of the murine TNF-α gene to repress transcription (162). In a similar manner, HSF1 represses transcription of the gene for IL-1β through physical interaction with the CCAAT/enhancer binding protein (163).…”

Section: Stress Proteins and Cytoprotectionmentioning

confidence: 99%

“…Recent studies suggest that HSF1 acts directly as a transciptional repressor of several proinflammatory proteins, including IL-1β, c-fos, urokinase, and TNF-α (162,163). For example, HSF1 binds the 5'-untranslated region of the murine TNF-α gene to repress transcription (162).…”

Section: Stress Proteins and Cytoprotectionmentioning

confidence: 99%

Heat shock response and acute lung injury☆

Wheeler

Wong

2007

Free Radical Biology and Medicine

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All cells respond to stress through the activation of primitive, evolutionarily conserved genetic programs that maintain homeostasis and assure cell survival. Stress adaptation, which is known in the literature by a myriad of terms, including tolerance, desensitization, conditioning, and reprogramming, is a common paradigm found throughout nature, in which a primary exposure of a cell or organism to a stressful stimulus (e.g., heat) results in an adaptive response by which a second exposure to the same stimulus produces a minimal response. More interesting is the phenomenon of cross-tolerance, by which a primary exposure to a stressful stimulus results in an adaptive response whereby the cell or organism is resistant to a subsequent stress that is different from the initial stress (i.e. exposure to heat stress leading to resistance to oxidant stress). The heat shock response is one of the more commonly described examples of stress adaptation and is characterized by the rapid expression of a unique group of proteins collectively known as heat shock proteins (also commonly referred to as stress proteins). The expression of heat shock proteins is well described in both whole lungs and in specific lung cells from a variety of species and in response to a variety of stressors. More importantly, in vitro data, as well as data from various animal models of acute lung injury, demonstrate that heat shock proteins, especially Hsp27, Hsp32, Hsp60, and Hsp70 have an important cytoprotective role during lung inflammation and injury.

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Heat Shock Factor 1 Represses Transcription of the IL-1β Gene through Physical Interaction with the Nuclear Factor of Interleukin 6

Cited by 163 publications

References 66 publications

ANG II promotes IGF-IIR expression and cardiomyocyte apoptosis by inhibiting HSF1 via JNK activation and SIRT1 degradation

ANG II promotes IGF-IIR expression and cardiomyocyte apoptosis by inhibiting HSF1 via JNK activation and SIRT1 degradation

Post-traumatic immunosuppression is reversed by anti-coagulated salvaged blood transfusion: deductions from studying immune status after knee arthroplasty

Heat shock response and acute lung injury☆

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