CYP1A1 Relieves Lipopolysaccharide-Induced Inflammatory Responses in Bovine Mammary Epithelial Cells

Zhang, Wen-Yao; Wang, Hao; Qi, Shao-pei; Wang, Xixi; Li, Xueru; Zhou, Kun; Zhang, Yong; Gao, Ming-Qing

doi:10.1155/2018/4093285

Cited by 17 publications

(15 citation statements)

References 37 publications

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“…With respect to molecular changes, we observed that while the expression of the majority of mRNAs increased in the tumor cells upon MΦ infiltration, CYP1A1 expression appeared to be inhibited. This corroborates previous findings that inflammatory conditions, induced by LPS or found during mastitis, suppress CYP1A1 expression in mammary epithelial cells [13]. In contrast to epithelial cells, enhanced CYP1A1 expression in response to LPS was shown in human dendritic cells [24].…”

Section: Discussionsupporting

confidence: 91%

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Macrophages attenuate the transcription of CYP1A1 in breast tumor cells and enhance their proliferation

et al. 2019

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While aberrant cells are routinely recognized and removed by immune cells, tumors eventually escape innate immune responses. Infiltrating immune cells are even corrupted by the tumor to acquire a tumor-supporting phenotype. In line, tumor-associated macrophages are well-characterized to promote tumor progression and high levels of tumor-infiltrating macrophages are a poor prognostic marker in breast cancer. Here, we aimed to further decipher the influence of macrophages on breast tumor cells and determined global gene expression changes in three-dimensional tumor spheroids upon infiltration of macrophages. While various tumor-associated mRNAs were upregulated, expression of the cytochrome P450 family member CYP1A1 was markedly attenuated. Repression of CYP1A1 in tumor cells was elicited by a macrophage-shaped tumor microenvironment rather than by direct tumor cell-macrophage contacts. In line with changes in RNA expression profiles, macrophages enhanced proliferation of the tumor cells. Enhanced proliferation and macrophage presence further correlated with reduced CYP1A1 expression in patient tumors when compared with normal tissue. These findings are of interest in the context of combinatory therapeutic approaches involving cytotoxic and immune-modulatory compounds.

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Section: Discussionsupporting

confidence: 91%

“…In line, polymorphisms associated with higher CYP1A1 activity have been associated with elevated breast cancer risk [10, 11]. Interestingly, CYP1A1 expression commonly appears to be repressed by inflammatory mediators [12, 13].…”

Section: Introductionmentioning

confidence: 99%

Macrophages attenuate the transcription of CYP1A1 in breast tumor cells and enhance their proliferation

et al. 2019

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“…S5B ). Moreover, VIPR1 , CYP1A1 and PPP1R14A are reported to be strongly associated with the modulation of inflammatory and/or innate immune responses as their downregulation results in the elevation of immune responses ( Abad et al., 2016 ; Blackham et al., 2010 ; Delgado et al., 2001 ; Fang et al., 2016 ; Paton and Renton, 1998 ; Yin et al., 2017 ; Zhang et al., 2018 ) during microbial infections, autoimmunity and dendritic cell differentiation respectively. Altogether, our result concludes that these metabolic pathways-related genes or cellular factors contributes in elevation of RNA virus infection and causing lung disease severity in presence of airborne ambient PM.…”

Section: Resultsmentioning

confidence: 99%

Particulate matter (PM10) enhances RNA virus infection through modulation of innate immune responses

Mishra

Krishnamoorthy

Gangamma

et al. 2020

Environmental Pollution

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Sensing of pathogens by specialized receptors is the hallmark of the innate immunity. Innate immune response also mounts a defense response against various allergens and pollutants including particulate matter present in the atmosphere. Air pollution has been included as the top threat to global health declared by WHO which aims to cover more than three billion people against health emergencies from 2019 to 2023. Particulate matter (PM), one of the major components of air pollution, is a significant risk factor for many human diseases and its adverse effects include morbidity and premature deaths throughout the world. Several clinical and epidemiological studies have identified a key link between the PM existence and the prevalence of respiratory and inflammatory disorders. However, the underlying molecular mechanism is not well understood. Here, we investigated the influence of air pollutant, PM 10 (particles with aerodynamic diameter less than 10 μm) during RNA virus infections using Highly Pathogenic Avian Influenza (HPAI) – H5N1 virus. We thus characterized the transcriptomic profile of lung epithelial cell line, A549 treated with PM 10 prior to H5N1infection, which is known to cause severe lung damage and respiratory disease. We found that PM 10 enhances vulnerability (by cellular damage) and regulates virus infectivity to enhance overall pathogenic burden in the lung cells. Additionally, the transcriptomic profile highlights the connection of host factors related to various metabolic pathways and immune responses which were dysregulated during virus infection. Collectively, our findings suggest a strong link between the prevalence of respiratory illness and its association with the air quality.

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“…Currently, no study in cattle has established the relative contribution of differing CYP450 to the overall oxylipid pool. Due to this, CYP450 that metabolize PUFA chosen for this study were selected based on their significant contribution to the oxylipid pool in other species, such as CYP2C19, CYP2E1, CY-P3A4, CYP4A11, and CYP4F2, or previous research in cattle that has explored the activity of a specific CYP450, such as CYP1A1 or CYP2J2 (Lasker et al, 2000;Yang et al, 2001;Fer et al, 2008;Zhang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Widespread basal cytochrome P450 expression in extrahepatic bovine tissues and isolated cells

Kühn

Putman

Sordillo

2020

Journal of Dairy Science

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Periparturient cattle face increased risk of both metabolic and infectious diseases. Factors contributing to this predisposition include oxidized polyunsaturated fatty acids, also known as oxylipids, whose production is altered during the periparturient period and in diseased cattle. Alterations in the production of oxylipids derived from cytochrome P450 (CYP450) enzymes are over-represented during times of increased disease risk and clinical disease, such as mastitis. Many of these same CYP450 enzymes additionally regulate metabolism of fat-soluble vitamins, such as A, D, and E. These vitamins are essential to maintaining immune health, yet circulating concentrations are diminished near calving. Despite this, a relatively small amount of research has focused on the roles of CYP450 enzymes outside of the liver. The aim of this paper is to describe the relative gene expression of 11 CYP450 in bovine tissues and common in vitro bovine cell models. Eight tissue samples were collected from 3 healthy dairy cows after euthanasia. In vitro samples included primary bovine aortic and mammary endothelial cells and immortalized bovine kidney and mammary epithelial cells. Quantitative real-time-PCR was carried out to assess basal transcript expression of CYP450 enzymes. Surprisingly, CYP450 mRNA was widely expressed in all tissue samples, with predominance in the liver. In vitro CYP450 expression was less robust, with several cell types lacking expression of specific CYP450 enzymes altogether. Overall, cell culture models did not reflect expression of tissue CYP450. However, when CYP450 were organized by activity, certain cell types consistently expressed specific functional groups. These data reveal the widespread expression of CYP450 in individual organs of healthy dairy cows. Widespread expression helps to explain previous evidence of significant changes in CYP450-mediated oxylipid production and fat-soluble vitamin metabolism in organ microenvi-ronments during periods of oxidative stress or disease. As such, these data provide a foundation for targeted functional experiments aimed at understanding the activities of specific CYP450 and associated therapeutic potential during times of increased disease risk.

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CYP1A1 Relieves Lipopolysaccharide-Induced Inflammatory Responses in Bovine Mammary Epithelial Cells

Cited by 17 publications

References 37 publications

Macrophages attenuate the transcription of CYP1A1 in breast tumor cells and enhance their proliferation

Macrophages attenuate the transcription of CYP1A1 in breast tumor cells and enhance their proliferation

Particulate matter (PM10) enhances RNA virus infection through modulation of innate immune responses

Widespread basal cytochrome P450 expression in extrahepatic bovine tissues and isolated cells

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