Heat shock protein 27 immune complex altered signaling and transport (ICAST): Novel mechanisms of attenuating inflammation

Shi, Chunhua; Deng, Jingjing; Chiu, Michael; Chen, Yong Xiang; O’Brien, Edward R.

doi:10.1096/fj.202001389rr

Cited by 23 publications

(22 citation statements)

References 30 publications

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“…Indeed, contrary to the expected, the pre-incubation of cells with an anti-GGT antibody amplified the TF procoagulant activity as compared to hrGGT per se. It is known that immunocomplexes can activate TLR4 [ 29 ]. Furthermore, monocytes express neonatal Fc receptor for IgG (FcRn) and Fc gamma receptor (FcγR) families whose activation by single IgG and, to a greater extent, immunocomplexes IgG activates TF gene transcription [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Binding of Gamma-Glutamyl Transferase to TLR4 Signalling Allows Tissue Factor Activation in Monocytes

Sanguinetti

Scalise

Neri

et al. 2022

IJMS

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Gamma-glutamyl transferase (GGT) is involved in the progression of atherosclerosis, since its enzymatic activity promotes the generation of reactive oxygen species (ROS). Besides, GGT may act as a prothrombotic factor by inducing tissue factor (TF) expression, independently of its enzymatic activity. The aim of this study was to assess whether GGT-induced TF stimulation was a consequence of binding to toll-like receptor 4 (TLR4) expressed on monocytes, the precursors of macrophages and foam cells which colocalize with GGT activity within atherosclerotic plaques. Experiments were performed in human peripheral blood mononuclear cells (PBMCs), THP-1 cells (a monocytic cellular model), and HEK293 cells, which were genetically modified to study the activation of TLR4. TF procoagulant activity was assessed by a one-stage clotting time test, and TF protein expression was estimated by western blot. Human recombinant (hr) GGT protein increased TF procoagulant activity and protein expression in both PBMCs and THP-1 cells. The GGT-induced TF stimulation was prevented by cellular pretreatment with TLR4/NF-κB inhibitors (LPS-Rs, CLI-095, and BAY-11-7082), and HEK293 cells lacking TLR4 confirmed that TLR4 is essential for GGT-induced activation of NF-κB. In conclusion, hrGGT induced TF expression in monocytes through a cytokine-like mechanism that involved the activation of TLR4/NF-κB signaling.

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Section: Discussionmentioning

confidence: 99%

Binding of Gamma-Glutamyl Transferase to TLR4 Signalling Allows Tissue Factor Activation in Monocytes

Sanguinetti

Scalise

Neri

et al. 2022

IJMS

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“…Consistent with this, Feng et al reported increased levels of sHSP27 in only 10% of CHB patients by proteome analysis [11]. Anti-HSP27-Ab not only is more stable and easily detectable in serum, but also might enhance the function of sHSP27 as an in ammatory modulator [13]. Therefore, anti-HSP27-Ab has recently received growing attention and reported to important role in many diseases such as cardiovascular diseases, obesity, and diabetes [9,15,16].…”

Section: Discussionmentioning

confidence: 89%

“…SHSP27 can evoke immune system reactions, resulting in anti-HSP27 antibody production (Anti-HSP27-Ab) [12]. More importantly, the creation of sHSP27 and anti-HSP27-Ab immune complexes have been reported to enhance the function of sHSP27 by altering the signaling of crucial receptors involved in the in ammatory processes [13]. As antibodies are simply measured by blood tests and are often more stable and easily detectable due to higher concentrations [14], recent studies seek to discover the role of circulating anti-HSP27-Ab in various diseases [9,15,16].…”

Section: Introductionmentioning

confidence: 99%

Association Between Serum Levels of Anti-heat Shock Protein 27 Antibody and Liver Cell Injury in Chronic Hepatitis B

Yousefli

Meshkat²,

Ghayour‐Mobarhan³

et al. 2023

Ind J Clin Biochem

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BackgroundHeat Shock Protein 27 (HSP27), an anti-HBV factor, exists in the intracellular and extracellular spaces. Serum HSP27 (sHSP27) is an in ammatory modulator and is associated with elevated pro-in ammatory cytokines and with a higher likelihood of hepatocellular carcinoma. SHSP27 results in natural antibody production (anti-HSP27-Ab) that is more stable and easily detectable compared to sHSP27. We aimed to investigate any potential association between anti-HSP27-Ab level and chronic hepatitis B (CHB) progression and in ammation indicated by liver cell injury and HBV replication. MethodsThis cross-sectional study was conducted on 91 patients with CHB and 92 individuals without CHB. Following demographic data collection, anti-HSP27-Ab, serum lipids including total cholesterol, triglyceride, LDL-C, HDL-C, and aminotransferase levels were measured using enzymatic assays in participants' serum samples. HBV DNA was also measured by quantitative PCR in CHB patients. ResultsBivariate and multivariate analyses showed a signi cantly higher mean level of anti-HSP27-Ab in CHB than in healthy individuals (0.304 vs. 0.256AU/ml, P-value = 0.015). These levels held signi cant differences in the CHB subgroups of male patients, at the age of 50 years and above, non-smokers, patients with elevated aminotransferase levels, and hypotriglyceridemia (P-value < 0.05). However, no difference was found between the antibody levels and HBV DNA copies (P-value > 0.05). ConclusionThis study provides evidence that anti-HSP27 antibody levels can re ect the degree of liver necrosis indicated by aminotransferase levels. Regarding the higher incidence rate of HBV-associated complications in 50 to 60-year-old men, monitoring the antibody can be bene cial in managing this group of CHB patients, which deserves further investigation.

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“…HSP27 immune complex activates TLR4/NF-κB signaling and increases the level of anti-inflammatory cytokine IL-10 in macrophages. Moreover, HSP27 immune complex reduces form cell formation by inhibiting oxidized low-density lipoprotein (oxLDL) binding to scavenger receptors ( 86 ). In addition, under ER stress, chaperone protein 78 kDa glucose-regulated protein (GRP78) dissociates from ER and moves to the cell surface, resulting in the generation of anti-GRP78 autoantibodies which activate NF-κB and induce the expression of adhesion molecules in human endothelial cells ( 87 ).…”

Section: The Nf-κb and Er Stress In Atherosclerosismentioning

confidence: 99%

NF-κB and its crosstalk with endoplasmic reticulum stress in atherosclerosis

Jin

Luo

et al. 2022

Front. Cardiovasc. Med.

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Atherosclerosis (AS) is a common cardiovascular disease with complex pathogenesis, in which multiple pathways and their interweaving regulatory mechanism remain unclear. The primary transcription factor NF-κB plays a critical role in AS via modulating the expression of a series of inflammatory mediators under various stimuli such as cytokines, microbial antigens, and intracellular stresses. Endoplasmic reticulum (ER) stress, caused by the disrupted synthesis and secretion of protein, links inflammation, metabolic signals, and other cellular processes via the unfolded protein response (UPR). Both NF-κB and ER stress share the intersection regarding their molecular regulation and function and are regarded as critical individual contributors to AS. In this review, we summarize the multiple interactions between NF-κB and ER stress activation, including the UPR, NLRP3 inflammasome, and reactive oxygen species (ROS) generation, which have been ignored in the pathogenesis of AS. Given the multiple links between NF-κB and ER stress, we speculate that the integrated network contributes to the understanding of molecular mechanisms of AS. This review aims to provide an insight into these interactions and their underlying roles in the progression of AS, highlighting potential pharmacological targets against the atherosclerotic inflammatory process.

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Heat shock protein 27 immune complex altered signaling and transport (ICAST): Novel mechanisms of attenuating inflammation

Cited by 23 publications

References 30 publications

Binding of Gamma-Glutamyl Transferase to TLR4 Signalling Allows Tissue Factor Activation in Monocytes

Binding of Gamma-Glutamyl Transferase to TLR4 Signalling Allows Tissue Factor Activation in Monocytes

Association Between Serum Levels of Anti-heat Shock Protein 27 Antibody and Liver Cell Injury in Chronic Hepatitis B

NF-κB and its crosstalk with endoplasmic reticulum stress in atherosclerosis

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