Heat shock proteins are no DAMPs, rather 'DAMPERs'

Broere, Femke; Zee, Ruurd van der; Eden, Willem van

doi:10.1038/nri2873-c1

Cited by 53 publications

(41 citation statements)

References 24 publications

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“…A large number of candidates including heat-shock proteins (HSPs), mitochondrial DNA, hyaluronan, formyl peptides, ATP, uric acid, S100B, and high-mobility group box 1 (HMGB1) have been suggested to act as DAMPs (5,7), but only a few of these molecules have a confirmed DAMP function in vivo. As such, HSPs were once considered key proinflammatory DAMPs, but have recently been suggested to dampen immune responses (8). Likewise, HMGB1 has been suggested to amplify inflammation rather than directly triggering it (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis

Huebener¹,

Pradère²,

Hernandez³

et al. 2014

J. Clin. Invest.

307

224

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Section: Introductionmentioning

confidence: 99%

The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis

Huebener¹,

Pradère²,

Hernandez³

et al. 2014

J. Clin. Invest.

307

224

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“…Transfer of these HSP-specific regulatory T cells inhibited inflammation in animal models of arthritis (60,62). A recent phase II clinical trial yielded promising results (65,66). This strategy illustrates how targeting the upstream components of the inflammatory cascade that leads to pathological cytokine production may offer a more effective strategy.…”

Section: Figurementioning

confidence: 96%

Alarmins: awaiting a clinical response

Chan

Roth²,

Oppenheim³

et al. 2012

J. Clin. Invest.

435

331

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“…Thus, as suggested by W. Van Eden for other HSP family members, HSP110 should therefore not be considered a DAMP (accordingly to the concept of "danger" introduced by P. Matzinger) but rather as a "DAMPer" of the immune system. 43 Several groups have investigated the nature of the immune infiltrate within tumors of CRC patients. Though all groups agree on the higher Th1 cell colonization, they provide puzzling observations regarding myeloid cells.…”

Section: E1170264-6mentioning

confidence: 99%

Extracellular HSP110 skews macrophage polarization in colorectal cancer

et al. 2016

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HSP110 is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps the cells to survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently showed that colorectal cancer (CRC) patients with microsatellite instability (MSI) had an improved response to chemotherapy because they harbor an HSP110 inactivating mutation (HSP110DE9). In this work, we have used patients' biopsies and human CRC cells grown in vitro and in vivo (xenografts) to demonstrate that (1) HSP110 is secreted by CRC cells and that the amount of this extracellular HSP110 is strongly decreased by the expression of the mutant HSP110DE9, (2) Supernatants from CRC cells overexpressing HSP110 or purified recombinant human HSP110 (LPS-free) affect macrophage differentiation/polarization by favoring a pro-tumor, anti-inflammatory profile, (3) Conversely, inhibition of HSP110 (expression of siRNA, HSP110DE9 or immunodepletion) induced the formation of macrophages with a cytotoxic, pro-inflammatory profile. (4) Finally, this effect of extracellular HSP110 on macrophages seems to implicate TLR4. These results together with the fact that colorectal tumor biopsies with HSP110 high were infiltrated with macrophages with a pro-tumoral profile while those with HSP110 low were infiltrated with macrophages with a cytotoxic profile, suggest that the effect of extracellular HSP110 function on macrophages may also contribute to the poor outcomes associated with HSP110 expression.

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Heat shock proteins are no DAMPs, rather 'DAMPERs'

Cited by 53 publications

References 24 publications

The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis

The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis

Alarmins: awaiting a clinical response

Extracellular HSP110 skews macrophage polarization in colorectal cancer

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