Induction of Gamma-Glutamyltransferase Activity and Consequent Pro-oxidant Reactions in Human Macrophages Exposed to Crocidolite Asbestos

Corti, Alessandro; Bonetti, Justine; Dominici, Silvia; Piaggi, Simona; Fierabracci, Vanna; Foddis, Rudy; Pompella, Alfonso

doi:10.1093/toxsci/kfz175

Cited by 6 publications

(5 citation statements)

References 30 publications

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“…It is well known that asbestos fibers can induce alterations in the immune system, while being involved in the inflammatory process 40 – 42 . Different studies have reported miR-197-3p as being significantly down-regulated in inflammatory conditions 43 .…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNA-197-3p as a potential biomarker for asbestos exposure

Frontini

Bononi

Torreggiani

et al. 2021

Sci Rep

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Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-qPCR and ddPCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n = 75) compared to HS (n = 62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p = 0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p = 0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.

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Section: Discussionmentioning

confidence: 99%

Circulating microRNA-197-3p as a potential biomarker for asbestos exposure

Frontini

Bononi

Torreggiani

et al. 2021

Sci Rep

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show abstract

“…It is well known that asbestos fibers can induce alterations in the immune system, while being involved in the inflammatory process [40][41][42] . Different studies have reported miR-197-3p as being significantly down-regulated in inflammatory conditions 43 .…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNA-197-3p as a potential biomarker for asbestos exposure

Frontini¹,

Bononi²,

Torreggiani³

et al. 2021

Preprint

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Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-PCR and dd-PCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n=75) compared to HS (n=62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p=0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p=0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.

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“…In addition to H 2 O 2 generated from NOX, another source of ROS in macrophages is identified as γ-glutamyltransferase (GGT), which is found in exposure to crocidolite and neuroinflammation. The oxidative injury and clinical signs in neuroinflammation can be suppressed by targeting GGT activity [ 86 , 87 ]. Compared with M1 macrophages, M2 macrophages have lower levels of ROS and hydrogen peroxide, which implies M1 types’ pro-inflammatory and M2 types’ anti-inflammatory functions [ 88 ] (Fig.…”

Section: Background Of Macrophagementioning

confidence: 99%

Interaction between macrophages and ferroptosis

et al. 2022

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Ferroptosis, a newly discovered iron-dependent cell death pathway, is characterized by lipid peroxidation and GSH depletion mediated by iron metabolism and is morphologically, biologically and genetically different from other programmed cell deaths. Besides, ferroptosis is usually found accompanied by inflammatory reactions. So far, it has been found participating in the development of many kinds of diseases. Macrophages are a group of immune cells that widely exist in our body for host defense and play an important role in tissue homeostasis by mediating inflammation and regulating iron, lipid and amino acid metabolisms through their unique functions like phagocytosis and efferocytosis, cytokines secretion and ROS production under different polarization. According to these common points in ferroptosis characteristics and macrophages functions, it’s obvious that there must be relationship between macrophages and ferroptosis. Therefore, our review aims at revealing the interaction between macrophages and ferroptosis concerning three metabolisms and integrating the application of certain relationship in curing diseases, mostly cancer. Finally, we also provide inspirations for further studies in therapy for some diseases by targeting certain resident macrophages in distinct tissues to regulate ferroptosis. Facts Ferroptosis is considered as a newly discovered form characterized by its nonapoptotic and iron-dependent lipid hydroperoxide, concerning iron, lipid and amino acid metabolisms. Ferroptosis has been widely found playing a crucial part in various diseases, including hepatic diseases, neurological diseases, cancer, etc. Macrophages are phagocytic immune cells, widely existing and owning various functions such as phagocytosis and efferocytosis, cytokines secretion and ROS production. Macrophages are proved to participate in mediating metabolisms and initiating immune reactions to maintain balance in our body. Recent studies try to treat cancer by altering macrophages’ polarization which damages tumor microenvironment and induces ferroptosis of cancer cells. Open questions How do macrophages regulate ferroptosis of other tissue cells specifically? Can we use the interaction between macrophages and ferroptosis in treating diseases other than cancer? What can we do to treat diseases related to ferroptosis by targeting macrophages? Is the use of the relationship between macrophages and ferroptosis more effective than other therapies when treating diseases?

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Induction of Gamma-Glutamyltransferase Activity and Consequent Pro-oxidant Reactions in Human Macrophages Exposed to Crocidolite Asbestos

Cited by 6 publications

References 30 publications

Circulating microRNA-197-3p as a potential biomarker for asbestos exposure

Circulating microRNA-197-3p as a potential biomarker for asbestos exposure

Circulating microRNA-197-3p as a potential biomarker for asbestos exposure

Interaction between macrophages and ferroptosis

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