Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury

Lee, Sang‐Min; McLaughlin, Joseph N.; Frederick, Daniel R.; Zhu, Lin; Thambiayya, Kalidasan; Wasserloos, Karla J.; Kaminski, Iris; Pearce, Linda L.; Peterson, Jim; Latoche, Joseph D.; Palmer, Octavia M. Peck; Stolz, Donna B.; Fattman, Cheryl L.; Alcorn, John F.; Oury, Tim D.; Angus, Derek C.; Pitt, Bruce R.; Kaynar, A. Murat

doi:10.1152/ajplung.00243.2012

Cited by 14 publications

(5 citation statements)

References 69 publications

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“…The beneficial effect of genetic Mt1 and Mt2 deletion on survival and disease progression in our colitis model has previously been reported in an Alzheimer's disease model, in the TNF‐induced lethal shock model, and in hyperoxic acute lung injury []. However, pro‐survival properties for MTs have also been described.…”

Section: Discussionmentioning

confidence: 64%

Role of metallothioneins as danger signals in the pathogenesis of colitis

Devisscher

Hindryckx

Lynes

et al. 2014

The Journal of Pathology

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Inflammatory bowel diseases (IBDs) are recurrent intestinal pathologies characterized by a compromised epithelial barrier and an exaggerated immune activation. Mediators of immune cell infiltration may represent new therapeutic opportunities. Metallothioneins (MTs) are stress-responsive proteins with immune-modulating functions. Metallothioneins have been linked to IBDs, but their role in intestinal inflammation is inconclusive. We investigated MT expression in colonic biopsies from IBDs and acute infectious colitis patients and healthy controls and evaluated MT's role in experimental colitis using MT knockout mice and anti-MT antibodies. Antibody potential to target extracellular MT and its mechanism was tested in vitro. Biopsies of patients with active colitis showed infiltration of MT-positive cells in a pattern that correlated with the grade of inflammation. MT knockout mice displayed less severe acute dextran sulphate sodium (DSS)-induced colitis compared to congenic wild-type mice based on survival, weight loss, colon length, histological inflammation and leukocyte infiltration. Chronic DSS-colitis confirmed that Mt1 and Mt2 gene disruption enhances clinical outcome. Blockade of extracellular MT with antibodies reduced F4/80-positive macrophage infiltration in DSS- and trinitrobenzene sulphonic acid-colitis, with a tendency towards a better outcome. Whole-body single-photon emission computer tomography of mice injected with radioactive anti-MT antibodies showed antibody accumulation in the colon during colitis and clearance during recovery. Necrotic and not apoptotic cell death resulted in western blot MT detection in HT29 cell supernatant. In a Boyden chamber migration assay, leukocyte attraction towards the necrotic cell supernatant could be abolished with anti-MT antibody, indicating the chemotactic potential of endogenous released MT. Our results show that human colitis is associated with infiltration of MT-positive inflammatory cells. Since antibody blockade of extracellular MT can reduce colitis in mice, MT may act as a danger signal and may represent a novel target for reducing leukocyte infiltration and inflammation in IBD patients.

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Section: Discussionmentioning

confidence: 64%

Role of metallothioneins as danger signals in the pathogenesis of colitis

Devisscher

Hindryckx

Lynes

et al. 2014

The Journal of Pathology

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“… 46 The inhibitory action of Zn on the replication of SARS-coronavirus is determined. 47 Zn deficiency resulted in an increase in proinflammatory cytokines that induce CS in COVID -19, including IL-6, IL-8, and TNF. 44 In the elderly, low zinc condition doubles the mortality rate, due to pneumonia.…”

Section: Discussionmentioning

confidence: 99%

Assessment of commitment to healthy daily habits and diets, preventive measures, and beliefs about natural products utilization during COVID-19 pandemic in certain population in Egypt and Saudi Arabia

El‐Malah¹,

Ibrahim²,

Attia³

et al. 2022

PHARMPRACT

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Objective: The purpose of this research is to assess the commitment of participants in Saudi Arabia and Egypt towards healthy daily habits, preventive measures, healthy food habits, and beliefs about natural products as an immunostimulants during COVID-19 pandemic. Method: A cross-sectional questionnaire-based study was conducted in Saudi Arabia (mainly Riyadh and Jeddah) and Egypt (mainly Cairo). The questionnaire instrument was created based on an extensive literature review on the COVID-19 pandemic, including its spreading and transmission methods, preventive measures, healthy lifestyle, and diets that increase human immunity against viral infections and the use of natural products and drinks. The questionnaire was created by Microsoft 365® office forms, participants were invited through emails and other social media. The questionnaire includes a demographic section (gender, nationality, residency country, city, age, marital status, educational level, employment status, chronic disease history, under anxiety or stress, have a temper or irritable person, were infected/currently infected and in contact to COVID-19 patient) and ( 23) questions arranged under five domains; Domain I daily habits (4), Domain II keeping preventive measures (4), Domain III healthy eating habits (9), Domain IV for participants currently or previously infected, or in contact with a patient (4) Domain V for assessment of participants' beliefs towards the use of natural products to elevate immunity during COVID-19 pandemic (2), beside 4 choice questions (stimulant drinks, natural drinks, natural products, and zinc-rich food). SPSS® was used to analyze the results using Student' t-test, ANOVA, and Tukey's HSD tests. Result: 510 individuals with various demographic characteristics participated in the study. This study revealed that the participants belief in healthy foods, natural drinks (mainly ginger, lemon, and cinnamon), natural products (mainly honey, olive oil, and black seed), healthy habits, and preventive measures as sanitizers, social distance, and exercise. Only 13% of all participants were infected with COVID-19, although 31% of them were in contact with COVID -19 patients, about 93% were under stress, and 22% were with chronic diseases. Participants who are married, not in contact with patients and not previously infected by COVID-19 are more adhered to preventive measures while those previously or currently infected are more committed to healthy lifestyle and diet habits. Qualification level seems to make no significant difference in any domain. 78.6% of the participants beliefs in the benefits of utilizing natural products in preventing infection with corona virus or reducing the period of treatment in case of infection. About 95.7% of the infected persons had no need of hospitalization and about 50% are cured within two weeks of infection. The questionnaire revealed that Nescafe and black tea were the most used stimulant drinks among the participants, particularly the students and who were always under stress. Most of the pa...

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“…Diluted solution concentrations were transformed to actual concentrations using the mass measurements recorded during dilution. Detection limits were down to 1 ppt (Lee et al., 2013 ). Analytical precision was assessed with sample duplicates.…”

Section: Methodsmentioning

confidence: 99%

Zinc deficiency enhances sensitivity to influenza A associated bacterial pneumonia in mice

Gopal,

Tutuncuoglu,

Bakalov

et al. 2024

Physiological Reports

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Although zinc deficiency (secondary to malnutrition) has long been considered an important contributor to morbidity and mortality of infectious disease (e.g. diarrhea disorders), epidemiologic data (including randomized controlled trials with supplemental zinc) for such a role in lower respiratory tract infection are somewhat ambiguous. In the current study, we provide the first preclinical evidence demonstrating that although diet‐induced acute zinc deficiency (Zn‐D: ~50% decrease) did not worsen infection induced by either influenza A (H1N1) or methicillin‐resistant staph aureus (MRSA), Zn‐D mice were sensitive to the injurious effects of superinfection of H1N1 with MRSA. Although the mechanism underlying the sensitivity of ZnD mice to combined H1N1/MRSA infection is unclear, it was noteworthy that this combination exacerbated lung injury as shown by lung epithelial injury markers (increased BAL protein) and decreased genes related to epithelial integrity in Zn‐D mice (surfactant protein C and secretoglobins family 1A member 1). As bacterial pneumonia accounts for 25%–50% of morbidity and mortality from influenza A infection, zinc deficiency may be an important pathology component of respiratory tract infections.

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Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury

Cited by 14 publications

References 69 publications

Role of metallothioneins as danger signals in the pathogenesis of colitis

Role of metallothioneins as danger signals in the pathogenesis of colitis

Assessment of commitment to healthy daily habits and diets, preventive measures, and beliefs about natural products utilization during COVID-19 pandemic in certain population in Egypt and Saudi Arabia

Zinc deficiency enhances sensitivity to influenza A associated bacterial pneumonia in mice

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