Mild hyperthermia modulates biological activities of interferons

Payne, Joseph E.; Nair, Madhavan; Ambrus, Julian L.; Chadha, Kailash C.

doi:10.1080/02656730050199340

Cited by 13 publications

(9 citation statements)

References 23 publications

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“…We have confirmed statistically significant differences in Dicer protein levels in normal human kidney cells in culture based on three independent experiments. Furthermore, fever range hyperthermia has also been shown to increase significantly the activity of both types of interferons [28], which we previously demonstrated to have post-transcriptional regulatory effects on Dicer [27]. However, whether Dicer variations have a role in the hyperthermia-induced augmentation of interferon antiviral activity has yet to be established.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we showed that Dicer could be regulated by cellular stresses and interferons as well as by modifications of genomic acetylation [27], factors known to contribute to the HSR [22, 28]. Moreover, enzymes downstream of Dicer, such as Argonaute 2 and other components of the RNA-induced silencing complex (RISC) were recently shown to be responsive to thermal stress [29] and dependent on the heat shock 70/90 machinery for their function [30].…”

Section: Introductionmentioning

confidence: 99%

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Mild hyperthermia enhances the expression and induces oscillations in the Dicer protein

Devasthanam

Tomasi

2013

International Journal of Hyperthermia

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Purpose To investigate whether mild heat stress at 39.5°C altered Dicer protein and miRNA expression patterns in several cell types. Methods Multiple human and mouse cell types were cultured during the course of 9 h at temperatures from 37°C to 39.5°C. Dicer mRNA levels and microRNAs were quantified by TaqMan RT-qPCR assays and Dicer protein by western blotting. Results Dicer protein was substantially elevated on western analysis in response to heat stress at 39.5°C in the absence of significant changes in Dicer mRNA by RT-qPCR. Conclusions Heat-induced regulation of Dicer expression occurs primarily post-transcriptionally, and the expression levels of Dicer protein are increased and often oscillate in response to fever-range hyperthermia in multiple mouse and human cells. Our studies suggest a potential role for Dicer and microRNAs in the response to mild thermal stress. Additional studies on the mechanisms involved in the stress-induced oscillations of Dicer protein and microRNAs will be of interest.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mild hyperthermia enhances the expression and induces oscillations in the Dicer protein

Devasthanam

Tomasi

2013

International Journal of Hyperthermia

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“…Interestingly, BRCA1 was found to interact with STAT1 and to mediate expression of target genes of the immune modulator interferon-g (Ouchi et al, 2000). Recent studies suggest that mild hyperthermia may enhance the antiviral and antiproliferative activity of interferon-g (Payne et al, 2000). However, the significance of a BRCA1 function in the heat shock response remains to be proven.…”

Section: Discussionmentioning

confidence: 99%

Role of BRCA1 in heat shock response

et al. 2003

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The heat shock response is an evolutionarily conserved response to heat and other stresses that promotes the maintenance of key metabolic functions and cell survival. We report that exposure of human prostate (DU-145) and breast (MCF-7) cancer cells to heat (421C) caused a rapid disappearance of the breast cancer susceptibility gene-1 (BRCA1) protein, starting at E1 h after the onset of heating and slightly lagging behind the increase in heat shock protein 70 (HSP70) levels. The heat-induced loss of BRCA1 occurred at the protein level, since: (1) BRCA1 mRNA expression was unaffected; and (2) the BRCA1 protein loss was also observed in DU-145 cells that expressed exogenous wild-type BRCA1 (wtBRCA1). In addition to heat regulation of BRCA1 protein levels, we also found that BRCA1 could modulate the heat shock response. Thus, wtBRCA1 overexpressing DU-145 cell clones showed significantly decreased sensitivity to heatinduced cytotoxicity; and Brca1 mutant mouse embryo fibroblasts showed increased sensitivity to heat. The DU-145 wtBRCA1 clones also showed increased expression of the small heat shock protein HSP27; and reporter assays revealed that wtBRCA1 stimulated a two to four-fold increase in HSP27 promoter activity, consistent with its ability to upregulate HSP27 mRNA and protein levels. In studies using epitope-tagged truncated BRCA1 proteins, the ability to stimulate the HSP27 promoter and to mediate heat-induced degradation required the aminoterminus but not the carboxyl-terminus of BRCA1. Although the heat-induced loss of BRCA1 appeared to be due to protein degradation, various protein metabolic agents (or combinations) failed to block this event, including: MG132 (a 26S proteasomal inhibitor), Nacetyl-leucyl-leucyl-norleucinal (a calpain inhibitor), z-VAD-fmk (a pan-caspase inhibitor), and ammonium chloride and chloroquine (which stabilize lysosomes). These findings suggest that in addition to its other functions, BRCA1 may participate in mammalian heat shock response pathways.

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“…The antiviral effect depends on the placement of hyperthermia as well as the duration of exposure. Applying hyperthermia for 4 h prior to the assay maximally increased antiviral activity compared to heating for 24 h. Interestingly, the activity of IFNs is increased with hyperthermia; however, application of hyperthermia after induction of human monocytes or fibroblasts decreased the actual production of IFN [83].…”

Section: Release Of Soluble Factors and Modulation Of Their Bioactivitymentioning

confidence: 91%

Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia

et al. 2009

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There is increasing documentation of significant survival benefits achieved in cancer patients treated with hyperthermia in combination with radiation and/or chemotherapy. Most evidence collected regarding the mechanisms by which hyperthermia positively influences tumor control has centered on in vitro data showing the ability of heat shock temperatures (usually above 42 degrees C) to result in radio- or chemosensitization. However, these high temperatures are difficult to achieve in vivo, and new thermometry data in patients reveal that much of the tumor and surrounding region is only heated to 40-41 degrees C or less as a result of vascular drainage from the target zone of the heated tumor. Thus, there is now a growing appreciation of a role for mild hyperthermia in the stimulation of various arms of the immune system in contributing to long term protection from tumor growth. Indeed, a review of recent literature suggests the existence of an array of thermally sensitive functions which may exist naturally to help the organism to establish a new "set point" of immune responsiveness during fever. This review summarizes recent literature identifying complex effects of temperature on immune cells and potential cellular mechanisms by which increased temperature may enhance immune surveillance.

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Mild hyperthermia modulates biological activities of interferons

Cited by 13 publications

References 23 publications

Mild hyperthermia enhances the expression and induces oscillations in the Dicer protein

Mild hyperthermia enhances the expression and induces oscillations in the Dicer protein

Role of BRCA1 in heat shock response

Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia

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