The Role of Cytochromes P450 in Infection

Stavropoulou, Elisavet; Pîrcălăbioru, Grațiela Grădișteanu; Bezirtzoglou, Eugenia

doi:10.3389/fimmu.2018.00089

Cited by 117 publications

(99 citation statements)

References 51 publications

(86 reference statements)

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“…Arachidonic acid is released from membrane phospholipids by phospholipases, and can be converted into pro-inflammatory prostaglandins via specific prostaglandin synthases and oxidases. Alternatively, it can be metabolized by Cyp (cytochrome P450) enzymes and lipoxygenases to anti-inflammatory hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) 26,27 . As shown in Fig.…”

Section: Plasminogen Treatment Of Radiation-induced Wounds Results Inmentioning

confidence: 99%

Plasminogen is a master regulator and a potential drug candidate for the healing of radiation wounds

Fallah

Viklund

Bäckman³

et al. 2020

Cell Death Dis

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Around 95% of cancer patients undergoing radiotherapy experience cutaneous side effects, and some develop radiation wounds or fibrosis. Currently, there is no effective treatment for these indications. We show here that plasminogen administration enhanced the healing of radiation wounds via pleiotropic effects on gene expression. Using RNA sequencing, we found that plasminogen downregulated the expression of genes in the TLR, TNF, WNT, MAPK, and TGF-β signaling pathways, and enhanced the anti-inflammatory effect of arachidonic acid, leading to significantly decreased inflammation and improved remodeling of granulation tissue compared with placebo treatment. In addition, plasminogen induced metabolic changes, including decreased glycolysis. Importantly, many of the factors downregulated by plasminogen are pro-fibrotic. Therefore, in radiation wounds with excessive inflammation, plasminogen is able to enhance and redirect the healing process, such that it more closely resembles physiological healing with significantly reduced risk for developing fibrosis. This makes plasminogen an attractive drug candidate for the treatment of radiation wounds in cancer patients.

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Section: Plasminogen Treatment Of Radiation-induced Wounds Results Inmentioning

confidence: 99%

Plasminogen is a master regulator and a potential drug candidate for the healing of radiation wounds

Fallah

Viklund

Bäckman³

et al. 2020

Cell Death Dis

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“…These selected genes are, VIPR1, mainly located on plasma membrane and PPP1R14A majorly located on nucleus and cytoskeleton were moderately found to be involved in virus infections like HIV-1 and influenza as reported by an in-vitro study and an in-silico phosphoproteomics study in human macrophages respectively [51-53]. CYP1A1 was recently reported to be involved in many virus infections especially hepatitis B and hepatitis C virus [54-56]. One such report superficially uncovers the induction of CYP1A1 in presences of PM 10 [57].…”

Section: Discussionmentioning

confidence: 99%

Imperative role of particulate matter in innate immunity during RNA virus infection

Mishra

Pandikannan

Gangamma

et al. 2020

Preprint

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25Sensing of pathogens by specialized receptors is the hallmark of the innate immune response. 26Innate immune response also mounts a defense response against various allergens and pollutants 27 including particulate matter present in the atmosphere. Air pollution has been included as the top 28 threat to global health declared by WHO which aims to cover more than three billion people against 29 health emergencies from 2019-2023. Particulate matter (PM), one of the major components of air 30 pollution, is a significant risk factor for many human diseases and its adverse effects include 31 morbidity and premature deaths throughout the world. Several clinical and epidemiological studies 32 have identified a key link between the PM composition and the prevalence of respiratory and 33 inflammatory disorders. However, the underlying molecular mechanism is not well understood. 34Here, we investigated the influence of air pollutant, PM10 during RNA virus infections using highly 35 pathogenic avian influenza (HPAI). We thus characterized the transcriptomic profile of lung 36 epithelial cell line, A549 treated with PM10 prior to infection with (HPAI) H5N1 influenza virus, 37 which is known to severely affect the lung and cause respiratory damage. We found that PM10 38 regulates virus infectivity and enhances overall pathogenic burden in the lung cells. Additionally, 39 the transcriptomic profile highlights the connection of host factors related to various metabolic 40 pathways and immune responses which were dysregulated during virus infection. Overall our 41 findings suggest a strong link between the prevalence of respiratory illness and the air quality. 42 43 44 45 Keywords: Particulate Matter (PM10), Virus Infection, Infectious Disease, Innate Immunity and 46 Metabolic Pathways-Related Genes. 47India and associated health concerns in term of occurrence of disease [14][15][16][17][18][19]. Although, most of 65 the studies were based on the epidemiological data and cross-sectional studies, there were few 66 studies about involvement of PM in respiratory diseases [20][21][22], asthma [23], cancer [24-27], 67 tuberculosis [28, 29] . It has been known that PM can induce innate immunity and can change the 68 level of cytokines, upon its exposure to the airways of humans [30][31][32][33]. PM were readily associated 69 with respiratory infections such as chronic obstructive pulmonary disease (COPD) [34][35][36][37] and it 70 is also reported to be associated with the respiratory syncytial virus (RSV) and influenza virus 71infections. [38][39][40][41]. Yet these studies are limited to epidemiological, cross -sectional studies [22, 72 42-44]. 73Here, we isolated and characterized PM10 from a heavily industrialized city Bengaluru, India and 74 checked its effect on RNA virus infection. We observed and concluded that PM10 hijacks the innate 75 immune system upon viral infection and significantly enhanced the viral replication of the RNA 76 viruses like new-castle disease virus (NDV), influenza virus -H1N1 (PR8) and H5N1. By 77...

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“…CYP proteins are known to metabolize a wide array of small molecules such as fatty acids, alkanes, and xenobiotic drugs. Recent studies have shown their involvement in microbial infections 85,86 . In our analysis, five CYP members (2A4, 2A5, 2E1, 4A10, and 4A14) were found to be significantly down-regulated in day-7 kidneys compared to day-2.…”

Section: Discovery-based Studies Recapitulate Signature Proteins For mentioning

confidence: 99%

“…For example, the expression of Cyp4a10 was dramatically increased after acute infection (at day 2) and declined back to the basal level at chronic stage (at day 7) ( Figure 6C). It has been noted that CYP enzymes can be selectively regulated in different states of inflammation by a multitude of cytokines released after infection or inflammation 85 . In hepatic and extrahepatic tissues, chronic inflammation is usually associated with downregulation of CYP enzymes 85 .…”

Section: Discovery-based Studies Recapitulate Signature Proteins For mentioning

confidence: 99%

“…It has been noted that CYP enzymes can be selectively regulated in different states of inflammation by a multitude of cytokines released after infection or inflammation 85 . In hepatic and extrahepatic tissues, chronic inflammation is usually associated with downregulation of CYP enzymes 85 . Hence, our quantitative data of CYP proteins were in line with previous studies and suggest that they could also be used as signatures for kidney disease severity and/or classification.…”

Section: Discovery-based Studies Recapitulate Signature Proteins For mentioning

confidence: 99%

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The global proteome and phosphoproteome landscape of sepsis-induced kidney injury

Lin

Platt

Zhou

et al. 2020

Preprint

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Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, while AKI has been recognized as a disease with long-term sequelae, partly due to the associated higher risk of chronic kidney disease (CKD), the understanding of kidney pathophysiology at the molecular level and the global view of dynamic regulations in situ after S-AKI, including transition to CKD, remains limited. Existing studies of S-AKI mainly focus on deriving sepsis biomarkers from body fluids. In the present study, we constructed a mid-severity septic murine model using cecal ligation and puncture (CLP), and examined the temporal changes to the kidney proteome and phosphoproteome at day 2 and day 7 after CLP surgery, corresponding to S-AKI and the transition to CKD, respectively by employing an ultrafast and economical filter-based sample processing method combined with the label-free quantitation approach. Collectively, we identified 2,119 proteins and 2,950 phosphosites through multi-proteomics analyses. Here we denote the pathways that are specifically responsive to S-AKI and its transition to CKD, which include regulation of cell metabolism regulation, oxidative stress, and energy consumption in the diseased kidneys. Our data can serve as an enriched resource for the identification of mechanisms and biomarkers for sepsis-induced kidney diseases.

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The Role of Cytochromes P450 in Infection

Cited by 117 publications

References 51 publications

Plasminogen is a master regulator and a potential drug candidate for the healing of radiation wounds

Plasminogen is a master regulator and a potential drug candidate for the healing of radiation wounds

Imperative role of particulate matter in innate immunity during RNA virus infection

The global proteome and phosphoproteome landscape of sepsis-induced kidney injury

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