The Anti-inflammatory Effects of Heat Shock Protein 72 Involve Inhibition of High-Mobility-Group Box 1 Release and Proinflammatory Function in Macrophages

Tang, Daolin; Kang, Rui; Xiao, Weimin; Wang, Haichao; Calderwood, Stuart K.; Xiao, Xianzhong

doi:10.4049/jimmunol.179.2.1236

Cited by 118 publications

(101 citation statements)

References 66 publications

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“…[42][43][44] It is well established that exogenous HMGB1 induces MEK-ERK activation in immune cells and cancer cells. 19,22,32,45 Here, we found that 3-MA inhibited HMGB1-induced phosphorylation of ERK, indicating that ERK is a downstream signal of PI3K. Importantly, knockdown or pharmacological inhibition of MEK-ERK attenuated HMGB1-induced LC3 conversion, suggesting that MEK-ERK is also required for HMGB1-induced autophagy in leukemia cells.…”

Section: Discussionmentioning

confidence: 64%

“…Before immunoprecipitation, samples containing equal amounts of proteins were pre-cleared with Protein A or protein G agarose/sepharose (Millipore) (4 1C, 3 h) and subsequently incubated with various irrelevant immunoglobulin-G or specific antibodies (5 mg/ml) in the presence of protein A or G agarose/sepharose beads for 2 h or overnight at 4 1C while gently shaking. 16,17,19 Following incubation, agarose/ sepharose beads were washed extensively with phosphatebuffered saline and proteins eluted by boiling in 2 Â SDS sample buffer before SDS-polyacrylamide gel electrophoresis.…”

Section: Immunoprecipitation Analysismentioning

confidence: 99%

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HMGB1-induced autophagy promotes chemotherapy resistance in leukemia cells

et al. 2010

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Autophagy, a tightly regulated lysosome-dependent catabolic pathway, is important in the regulation of cancer development and progression and in determining the response of tumor cells to anticancer therapy. However, the role of autophagy in leukemia still remains largely unknown. Here we show that high-mobility group box 1 (HMGB1), the best characterized damage-associated molecular pattern, was released from leukemia cell lines after chemotherapy-induced cytotoxicity and activated autophagy to protect against injury. Treatment with HMGB1-neutralizing antibodies increased the sensitivity of leukemia cells to chemotherapy; whereas, exogenous HMGB1 rendered these cells more resistant to drug-induced cytotoxicity. Moreover, exogenous HMGB1 increased autophagy as evaluated by increased expression of the autophagic marker microtubule-associated protein light chain 3-II, degradation of sequestosome 1 (p62) and autophagosome formation. Furthermore, knockdown or pharmacological inhibition of either phosphoinositide 3-kinase-III or extracellular signal-regulated kinase kinase mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase inhibited HMGB1-induced autophagy. Taken together, these results suggest that HMGB1 release after chemotherapy is a critical regulator of autophagy and a potential drug target for therapeutic interventions in leukemia.

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Section: Discussionmentioning

confidence: 64%

Section: Immunoprecipitation Analysismentioning

confidence: 99%

HMGB1-induced autophagy promotes chemotherapy resistance in leukemia cells

et al. 2010

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“…Proteins in cell lysates were first resolved by SDS-polyacrylamide gel electrophoresis and then transferred to nitrocellulose membrane and subsequently incubated with the primary antibody as previously described (20). After incubation with peroxidase-conjugated secondary antibodies, the signals were visualized using enhanced chemiluminescence according to the manufacturer's instruction.…”

Section: Western Blot Analysismentioning

confidence: 99%

Plumbagin Protects Mice from Lethal Sepsis by Modulating Immunometabolism Upstream of PKM2

Zhang

Deng

Kang

et al. 2016

Mol Med

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Sepsis is characterized by dysregulated systemic inflammation with release of early (for example, interleukin (IL)-1β) and late (for example, HMGB1) proinflammatory mediators from macrophages. Plumbagin, a medicinal plant-derived naphthoquinone, has been reported to exhibit antiinflammatory activity, but the underling mechanisms remain unclear. Here, we have demonstrated that plumbagin inhibits the inflammatory response through interfering with the immunometabolism pathway in activated macrophages. Remarkably, plumbagin inhibited lipopolysaccharide (LPS)-induced aerobic glycolysis by downregulating the expression of pyruvate kinase M2 (PKM2), a protein kinase responsible for the final and rate-limiting reaction step of the glycolytic pathway. Moreover, the NADPH oxidase 4 (NOX4)-mediated oxidative stress was required for LPS-induced PKM2 expression, because pharmacologic or genetic inhibition of NOX4 by plumbagin or RNA interference limited LPS-induced PKM2 expression, lactate production and subsequent proinflammatory cytokine (IL-1β and HMGB1) release in macrophages. Finally, plumbagin protected mice from lethal endotoxemia and polymicrobial sepsis induced by cecal ligation and puncture. These findings identify a new approach for inhibiting the NOX4/PKM2-dependent immunometabolism pathway in the treatment of sepsis and inflammatory diseases.

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“…For example, HSP70 has an anti-inflammatory activity by means of its inhibition of nuclear factor kappa B (NF-B) and a resulting suppression of pro-inflammatory cytokine and chemokine expression (23)(24)(25)(26). HSP70 has been reported to stimulate base excision repair, possibly by activation of human AP endonuclease and DNA polymerase ␤ (27)(28)(29).…”

mentioning

confidence: 99%

Prevention of UVB Radiation-induced Epidermal Damage by Expression of Heat Shock Protein 70

Matsuda

Hoshino

Yamashita

et al. 2010

Journal of Biological Chemistry

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Irradiation with UV light, especially UVB, causes epidermal damage via the induction of apoptosis, inflammatory responses, and DNA damage. Various stressors, including UV light, induce heat shock proteins (HSPs) and the induction, particularly that of HSP70, provides cellular resistance to such stressors. The anti-inflammatory activity of HSP70, such as its inhibition of nuclear factor kappa B (NF-B), was recently revealed. These in vitro results suggest that HSP70 protects against UVB-induced epidermal damage. Here we tested this idea by using transgenic mice expressing HSP70 and cultured keratinocytes. Irradiation of wild-type mice with UVB caused epidermal damage such as induction of apoptosis, which was suppressed in transgenic mice expressing HSP70. UVB-induced apoptosis in cultured keratinocytes was suppressed by overexpression of HSP70. Irradiation of wild-type mice with UVB decreased the cutaneous level of IB-␣ (an inhibitor of NF-B) and increased the infiltration of leukocytes and levels of pro-inflammatory cytokines and chemokines in the epidermis. These inflammatory responses were suppressed in transgenic mice expressing HSP70. In vitro, the overexpression of HSP70 suppressed the expression of pro-inflammatory cytokines and chemokines and increased the level of IB-␣ in keratinocytes irradiated with UVB. UVB induced an increase in cutaneous levels of cyclobutane pyrimidine dimers and 8-hydroxy-2-deoxyguanosine, both of which were suppressed in transgenic mice expressing HSP70. This study provides genetic evidence that HSP70 protects the epidermis from UVB-induced radiation damage. The findings here also suggest that the protective action of HSP70 is mediated by anti-apoptotic, anti-inflammatory, and anti-DNA damage effects.The skin can be structurally classified into several layers, including the most apical layer, the epidermis, containing large numbers of keratinocytes, and a second layer, immediately under this, the dermis, which has a high fibroblast content (1). Skin provides a major interface between the environment and the body and is constantly exposed to an array of physical and chemical stressors. Therefore, in addition to intrinsic causes, harmful exogenous causes are involved in the process of skin damage. Among exogenous harmful agents, UV irradiation is the most relevant to skin damage (photo-damage). UV light can be separated, based on wavelength, into three categories: UVA (320 -400 nm), UVB (290 -320 nm), and UVC (100 -290 nm). Of these, the celldamaging effect of UVA is relatively weak, whereas most UVC is absorbed by the ozone layer (2). Thus, UVB seems to play the central role in photo-damage, such as clinical sunburn, hyperpigmentation, erythema, plaque-like thickening, loss of skin tone, deep furrowing, and fine wrinkle formation, all of which constitute both clinical and cosmetic problems. Furthermore, UVB irradiation induces the development of skin cancer (photo-carcinogenesis) (3). UVB-induced photodamage and photo-carcinogenesis both involve epidermal damage (such as induction...

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The Anti-inflammatory Effects of Heat Shock Protein 72 Involve Inhibition of High-Mobility-Group Box 1 Release and Proinflammatory Function in Macrophages

Cited by 118 publications

References 66 publications

HMGB1-induced autophagy promotes chemotherapy resistance in leukemia cells

HMGB1-induced autophagy promotes chemotherapy resistance in leukemia cells

Plumbagin Protects Mice from Lethal Sepsis by Modulating Immunometabolism Upstream of PKM2

Prevention of UVB Radiation-induced Epidermal Damage by Expression of Heat Shock Protein 70

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