Immunosuppressive role of Benzo[a]pyrene in induction of lung cancer in mice

Salem, Mohamed L.; El-Ashmawy, Nahla E.; El-Fattah, Eslam E. Abd; Khedr, Eman G.

doi:10.1016/j.cbi.2020.109330

Cited by 24 publications

(8 citation statements)

References 37 publications

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“…Immunotoxic adverse effects exerted by many xenobiotics can hardly be recognized in healthy animals due to the fact that acute toxic effects become apparent only in relatively high doses [ 35 ]. Thus, immunotoxic effects of BaP reported in the literature were observed at higher doses up to 50 mg/kg body weight [ 35 , 36 ]. Moreover, the normal immune status in healthy individuals is commonly not very fragile; hence, strong adverse effects are needed to alter immune functions at baseline.…”

Section: Discussionmentioning

confidence: 99%

Aryl Hydrocarbon Receptor Activation by Benzo[a]pyrene Prevents Development of Septic Shock and Fatal Outcome in a Mouse Model of Systemic Salmonella enterica Infection

Fueldner

Riemschneider

Haupt

et al. 2022

Cells

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This study focused on immunomodulatory effects of aryl hydrocarbon receptor (AhR) activation through benzo[a]pyrene (BaP) during systemic bacterial infection. Using a well-established mouse model of systemic Salmonella enterica (S.E.) infection, we studied the influence of BaP on the cellular and humoral immune response and the outcome of disease. BaP exposure significantly reduced mortality, which is mainly caused by septic shock. Surprisingly, the bacterial burden in BaP-exposed surviving mice was significantly higher compared to non-exposed mice. During the early phase of infection (days 1-3 post-infection (p.i.)), the transcription of proinflammatory factors (i.e., IL-12, IFN-γ, TNF-α, IL-1β, IL-6, IL-18) was induced faster under BaP exposure. Moreover, BaP supported the activity of antigen-presenting cells (i.e., CD64 (FcγRI), MHC II, NO radicals, phagocytosis) at the site of infection. However, early in infection, the anti-inflammatory cytokines IL-10 and IL-22 were also locally and systemically upregulated in BaP-exposed S.E.-infected mice. BaP-exposure resulted in long-term persistence of salmonellae up to day 90 p.i., which was accompanied by significantly elevated S.E.-specific antibody responses (i.e., IgG1, IgG2c). In summary, these data suggest that BaP-induced AhR activation is capable of preventing a fatal outcome of systemic S.E. infection, but may result in long-term bacterial persistence, which, in turn, may support the development of chronic inflammation.

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Section: Discussionmentioning

confidence: 99%

Aryl Hydrocarbon Receptor Activation by Benzo[a]pyrene Prevents Development of Septic Shock and Fatal Outcome in a Mouse Model of Systemic Salmonella enterica Infection

Fueldner

Riemschneider

Haupt

et al. 2022

Cells

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“…Tobacco smoke includes many carcinogens, such as PAH, N-Nitrosamines including NNK, aza-arenes, aromatic amines, heterocyclic amines, aldehydes, miscellaneous organic compounds, and inorganic compounds [28]. N-nitrosodiethylamine (DEN) an N-Nitrosoamine [29][30][31], and benzo[a]pyrene (BaP), a PAH [32,33], are well-known carcinogens in tobacco smoke and induce carcinoma in almost all human tissues, including the lungs, mouth, throat, larynx, esophagus, stomach, colon, kidneys, liver, pancreas, cervix, bladder, and blood. However, tobacco smoke inhalation assays in laboratory animals show low incidence of pulmonary tumor formation, and most of the tumors are adenomas with the occasional adenocarcinoma as opposed to the highly invasive squamous cell carcinoma seen in human smokers [34].…”

Section: Rodent Models Of Lung Tumorigenesis 21 Rodent Lung Tumor Mod...mentioning

confidence: 99%

“…Therefore, the effects of heat-not-burn products on lung carcinogenesis need to be investigated in the future. Furthermore, BaP has an immunosuppressive role as evidenced by increased expression of TGF-β, CTLA-4, PD-L1, and FOXP3 and decreased expression of IL-12 in the lungs of BaP-treated mice as well as the increase in CD166 + cancer stem-like cells in the mice lungs [33]. Thus, in COPD-associated lung cancer mouse model, the immunosuppressive microenvironment could be related to tumor formation and progression [136,137].…”

Section: Lung Carcinogenesis and Chronic Inflammation In Rodent Modelsmentioning

confidence: 99%

Relationship between Lung Carcinogenesis and Chronic Inflammation in Rodents

Nakano‐Narusawa

Yokohira

Yamakawa

et al. 2021

Cancers

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Lung cancer remains the leading cause of cancer-related deaths, with an estimated 1.76 million deaths reported in 2018. Numerous studies have focused on the prevention and treatment of lung cancer using rodent models. Various chemicals, including tobacco-derived agents induce lung cancer and pre-cancerous lesions in rodents. In recent years, transgenic engineered rodents, in particular, those generated with a focus on the well-known gene mutations in human lung cancer (KRAS, EGFR, and p53 mutations) have been widely studied. Animal studies have revealed that chronic inflammation significantly enhances lung carcinogenesis, and inhibition of inflammation suppresses cancer progression. Moreover, the reduction in tumor size by suppression of inflammation in animal experiments suggests that chronic inflammation influences the promotion of tumorigenesis. Here, we review rodent lung tumor models induced by various chemical carcinogens, including tobacco-related carcinogens, and transgenics, and discuss the roles of chronic inflammation in lung carcinogenesis.

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“…Prostaglandin E2, the oncogene c-KIT, and the tumor suppressor Bin1 are all IDO1 modulators. Wnt5 also controls IDO1 activity in DC via β-catenin signaling while maintaining continuous expression in several cancer cell lines via an AhR-IL-6-STAT3 (Signal Transducer And Activator Of Transcription 3) signaling loop, according to new research [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

IDO/kynurenine pathway in cancer: possible therapeutic approaches

El-Fattah

2022

J Transl Med

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Cancer is one of the leading causes of death in both men and women worldwide. One of the main changes associated with cancer progression, metastasis, recurrence, and chemoresistance is the change in the tumor immune microenvironment, especially immunosuppression. Cancer immunosuppression appears in multiple forms, such as inhibition of immuno-stimulant cells with downregulation of immuno-stimulant mediators or through stimulation of immuno-suppressive cells with upregulation of immunosuppressive mediators. One of the most immunosuppressive mediators that approved potency in lung cancer progression is indoleamine 2,3-dioxygenase (IDO) and its metabolite kynurenine (Kyn). The current review tries to elucidate the role of IDO/Kyn on cancer proliferation, apoptosis, angiogenesis, oxidative stress, and cancer stemness. Besides, our review investigates the new therapeutic modalities that target IDO/Kyn pathway and thus as drug candidates for targeting lung cancer and drugs that potentiate IDO/Kyn pathway and thus can be cancer-promoting agents.

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Immunosuppressive role of Benzo[a]pyrene in induction of lung cancer in mice

Cited by 24 publications

References 37 publications

Aryl Hydrocarbon Receptor Activation by Benzo[a]pyrene Prevents Development of Septic Shock and Fatal Outcome in a Mouse Model of Systemic Salmonella enterica Infection

Aryl Hydrocarbon Receptor Activation by Benzo[a]pyrene Prevents Development of Septic Shock and Fatal Outcome in a Mouse Model of Systemic Salmonella enterica Infection

Relationship between Lung Carcinogenesis and Chronic Inflammation in Rodents

IDO/kynurenine pathway in cancer: possible therapeutic approaches

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