Hypochlorous acid-modified human serum albumin suppresses MHC class II - dependent antigen presentation in pro-inflammatory macrophages

Ulfig, Agnes; Bader, Verian; Varatnitskaya, Marharyta; Lupilov, Natalie; Winklhofer, Konstanze F.; Leichert, Lars I.

doi:10.1016/j.redox.2021.101981

Cited by 16 publications

(12 citation statements)

References 89 publications

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“…A more important part of this study was to comprehensively clarify the immunological role of NAPSB in HCC immune microenvironment. MHC molecules represent antigen presentation and processing capacity, and chemokines and receptors recruit effector TIICs [ 52 , 53 ], which may upregulate the activities of the cancer-immunity cycle subsequently [ 54 ]. In our study, NAPSB was found to be positively correlated with these immunomodulators, suggesting that NAPSB promoted immune activation, which was consistent with the results of enrichment analyses above.…”

Section: Discussionmentioning

confidence: 99%

NAPSB as a predictive marker for prognosis and therapy associated with an immuno-hot tumor microenvironment in hepatocellular carcinoma

Ning

Lin

et al. 2022

BMC Gastroenterol

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Background Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. However, the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined. Methods The expression of NAPSB in HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in patients with HCC using the Zhongnan cohort. Kaplan–Meier analyses, and univariate and multivariate Cox regression were conducted to determine the prognosis value of NAPSB on patients with HCC. Then enrichment analyses were performed to identify the possible biological functions of NAPSB. Subsequently, the immunological characteristics of NAPSB in the HCC tumor microenvironment (TME) were demonstrated comprehensively. The role of NAPSB in predicting hot tumors and its impact on immunotherapy and chemotherapy responses was also analyzed by bioinformatics methods. Results NAPSB was downregulated in patients with HCC and high NAPSB expression showed an improved survival outcome. Enrichment analyses showed that NAPSB was related to immune activation. NAPSB was positively correlated with immunomodulators, tumor-infiltrating immune cells, T cell inflamed score and cancer-immunity cycle, and highly expressed in immuno-hot tumors. High expression of NAPSB was sensitive to immunotherapy and chemotherapy, possibly due to its association with pyroptosis, apoptosis and necrosis. Conclusions NAPSB was correlated with an immuno-hot and inflamed TME, and tumor cell death. It can be utilized as a promising predictive marker for prognosis and therapy in HCC.

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Section: Discussionmentioning

confidence: 99%

NAPSB as a predictive marker for prognosis and therapy associated with an immuno-hot tumor microenvironment in hepatocellular carcinoma

Ning

Lin

et al. 2022

BMC Gastroenterol

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“…IL-6, IKK) and mediators of tissue remodeling (e.g. MMP7, TIMP-1), causing effects that are mostly consistent with modulation, attenuation, and resolution of inflammatory tissue responses (35,(80)(81)(82)(83)(84)(85)(86)(87)(88)(89). Specifically, inactivation of IKK (inhibitor of IkB kinase) through oxidation (Cys114/115) is thought to cause the hypochlorite-dependent attenuation of psoriasis observable upon topical application (35).…”

Section: Biomolecular Targets Of Chlorination Stress: From Chemical M...mentioning

confidence: 99%

Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer

2022

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A multitude of extrinsic environmental factors (referred to in their entirety as the ‘skin exposome’) impact structure and function of skin and its corresponding cellular components. The complex (i.e. additive, antagonistic, or synergistic) interactions between multiple extrinsic (exposome) and intrinsic (biological) factors are important determinants of skin health outcomes. Here, we review the role of hypochlorous acid (HOCl) as an emerging component of the skin exposome serving molecular functions as an innate immune factor, environmental toxicant, and topical chemopreventive agent targeting solar UV-induced skin cancer. HOCl [and its corresponding anion (OCl-; hypochlorite)], a weak halogen-based acid and powerful oxidant, serves two seemingly unrelated molecular roles: (i) as an innate immune factor [acting as a myeloperoxidase (MPO)-derived microbicidal factor] and (ii) as a chemical disinfectant used in freshwater processing on a global scale, both in the context of drinking water safety and recreational freshwater use. Physicochemical properties (including redox potential and photon absorptivity) determine chemical reactivity of HOCl towards select biochemical targets [i.e. proteins (e.g. IKK, GRP78, HSA, Keap1/NRF2), lipids, and nucleic acids], essential to its role in innate immunity, antimicrobial disinfection, and therapeutic anti-inflammatory use. Recent studies have explored the interaction between solar UV and HOCl-related environmental co-exposures identifying a heretofore unrecognized photo-chemopreventive activity of topical HOCl and chlorination stress that blocks tumorigenic inflammatory progression in UV-induced high-risk SKH-1 mouse skin, a finding with potential implications for the prevention of human nonmelanoma skin photocarcinogenesis.

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“…MPO protection against self-inactivation is a necessary process that prevents HOCl mediated MPO heme destruction, therefore allowing the enzyme to function at full capacity in generating HOCl [ 53 ]. One potential pathway of preventing MPO auto-inactivation is the rapid consumption of HOCl through rapid reaction with human serum albumin (HSA) and other proteins found in blood and other bodily fluids [ 56 ]. However, during COVID-19-associated inflammation, HSA and other HOCl scavengers suffer from decreased effectiveness due to competitive binding of SARS-COV-2, and HOCl production already exacerbated by inflammatory mediators is further unchecked [ 57 , 58 ].…”

Section: Hocl-associated Hemoprotein Heme Destructionmentioning

confidence: 99%

Melatonin interferes with COVID-19 at several distinct ROS-related steps

Camp

Bai

Gonullu

et al. 2021

Journal of Inorganic Biochemistry

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Recent studies have shown a correlation between COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the distinct, exaggerated immune response titled “cytokine storm”. This immune response leads to excessive production and accumulation of reactive oxygen species (ROS) that cause clinical signs characteristic of COVID-19 such as decreased oxygen saturation, alteration of hemoglobin properties, decreased nitric oxide (NO) bioavailability, vasoconstriction, elevated cytokines, cardiac and/or renal injury, enhanced D-dimer, leukocytosis, and an increased neutrophil to lymphocyte ratio. Particularly, neutrophil myeloperoxidase (MPO) is thought to be especially abundant and, as a result, contributes substantially to oxidative stress and the pathophysiology of COVID-19. Conversely, melatonin, a potent MPO inhibitor, has been noted for its anti-inflammatory, anti-oxidative, anti-apoptotic, and neuroprotective actions. Melatonin has been proposed as a safe therapeutic agent for COVID-19 recently, having been given with a US Food and Drug Administration emergency authorized cocktail, REGEN-COV2, for management of COVID-19 progression. This review distinctly highlights both how the destructive interactions of HOCl with tetrapyrrole rings may contribute to oxygen deficiency and hypoxia, vitamin B12 deficiency, NO deficiency, increased oxidative stress, and sleep disturbance, as well as how melatonin acts to prevent these events, thereby improving COVID-19 prognosis.

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Hypochlorous acid-modified human serum albumin suppresses MHC class II - dependent antigen presentation in pro-inflammatory macrophages

Cited by 16 publications

References 89 publications

NAPSB as a predictive marker for prognosis and therapy associated with an immuno-hot tumor microenvironment in hepatocellular carcinoma

NAPSB as a predictive marker for prognosis and therapy associated with an immuno-hot tumor microenvironment in hepatocellular carcinoma

Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer

Melatonin interferes with COVID-19 at several distinct ROS-related steps

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