Rapamycin Alleviates 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Aggravated Dermatitis in Mice with Imiquimod-Induced Psoriasis-Like Dermatitis by Inducing Autophagy

Kim, Hye Ran; Kim, Jin Cheol; Kang, Seok Young; Park, Chun Wook; Chung, Bo Young

doi:10.3390/ijms22083968

Cited by 22 publications

(17 citation statements)

References 61 publications

(71 reference statements)

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“…In turn, activation of Nrf2/HO-1 by TGN also inhibits activation of NF-κB and STAT3 which are the key transcription factors in psoriasis pathogenesis and promote the skin defense system while reducing the expression of immune mediators and epidermal proliferation (Lee et al, 2020). Further proving our subject, 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD) aggravated IMQ-induced psoriasis by increasing the expression of phosphorylated NF-κB p65 and inhibiting the antioxidant marker Nrf2 (Kim et al, 2021). These studies have provided a novel and clinically meaningful perspective on the pathogenesis and therapeutic targets of psoriasis in the world.…”

Section: Imiquimod (Imq)-induced Psoriasismentioning

confidence: 63%

Dissecting the Crosstalk Between Nrf2 and NF-κB Response Pathways in Drug-Induced Toxicity

Gao

Guo

Yang

et al. 2022

Front. Cell Dev. Biol.

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Nrf2 and NF-κB are important regulators of the response to oxidative stress and inflammation in the body. Previous pharmacological and genetic studies have confirmed crosstalk between the two. The deficiency of Nrf2 elevates the expression of NF-κB, leading to increased production of inflammatory factors, while NF-κB can affect the expression of downstream target genes by regulating the transcription and activity of Nrf2. At the same time, many therapeutic drug-induced organ toxicities, including hepatotoxicity, nephrotoxicity, cardiotoxicity, pulmonary toxicity, dermal toxicity, and neurotoxicity, have received increasing attention from researchers in clinical practice. Drug-induced organ injury can destroy body function, reduce the patients’ quality of life, and even threaten the lives of patients. Therefore, it is urgent to find protective drugs to ameliorate drug-induced injury. There is substantial evidence that protective medications can alleviate drug-induced organ toxicity by modulating both Nrf2 and NF-κB signaling pathways. Thus, it has become increasingly important to explore the crosstalk mechanism between Nrf2 and NF-κB in drug-induced toxicity. In this review, we summarize the potential molecular mechanisms of Nrf2 and NF-κB pathways and the important effects on adverse effects including toxic reactions and look forward to finding protective drugs that can target the crosstalk between the two.

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Section: Imiquimod (Imq)-induced Psoriasismentioning

confidence: 63%

Dissecting the Crosstalk Between Nrf2 and NF-κB Response Pathways in Drug-Induced Toxicity

Gao

Guo

Yang

et al. 2022

Front. Cell Dev. Biol.

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“…It is known that metformin and rapamycin treatments are able to extend the healthspan and lifespan of mice [ 216 , 217 ]. Interestingly, there is clear evidence that metformin and rapamycin can suppress AhR signaling in different models [ 218 , 219 ]. It seems that autophagy is involved in these results since both metformin and rapamycin are potent inducers of autophagy and it is known that autophagy is an important regulator of the aging process [ 52 , 107 ].…”

Section: Anti-aging Therapeutic Treatments Suppress Ahr Signalingmentioning

confidence: 99%

Aryl hydrocarbon receptor (AhR) reveals evidence of antagonistic pleiotropy in the regulation of the aging process

Salminen

2022

Cell. Mol. Life Sci.

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The antagonistic pleiotropy hypothesis is a well-known evolutionary theory to explain the aging process. It proposes that while a particular gene may possess beneficial effects during development, it can exert deleterious properties in the aging process. The aryl hydrocarbon receptor (AhR) has a significant role during embryogenesis, but later in life, it promotes several age-related degenerative processes. For instance, AhR factor (i) controls the pluripotency of stem cells and the stemness of cancer stem cells, (ii) it enhances the differentiation of embryonal stem cells, especially AhR signaling modulates the differentiation of hematopoietic stem cells and progenitor cells, (iii) it also stimulates the differentiation of immunosuppressive Tregs, Bregs, and M2 macrophages, and finally, (iv) AhR signaling participates in the differentiation of many peripheral tissues. On the other hand, AhR signaling is involved in many processes promoting cellular senescence and pathological processes, e.g., osteoporosis, vascular dysfunction, and the age-related remodeling of the immune system. Moreover, it inhibits autophagy and aggravates extracellular matrix degeneration. AhR signaling also stimulates oxidative stress, promotes excessive sphingolipid synthesis, and disturbs energy metabolism by catabolizing NAD+ degradation. The antagonistic pleiotropy of AhR signaling is based on the complex and diverse connections with major signaling pathways in a context-dependent manner. The major regulatory steps include, (i) a specific ligand-dependent activation, (ii) modulation of both genetic and non-genetic responses, (iii) a competition and crosstalk with several transcription factors, such as ARNT, HIF-1α, E2F1, and NF-κB, and (iv) the epigenetic regulation of target genes with binding partners. Thus, not only mTOR signaling but also the AhR factor demonstrates antagonistic pleiotropy in the regulation of the aging process.

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“…The mTOR inhibitor rapamycin is associated with the regulation of autophagy [ 109 ] and the dysfunction of which could contribute to the pathogenesis of psoriasis [ 110 ]. Rapamycin restored suppressed autophagy and increased AHR expression by PAH, 2,3,7,8-tetrachlorodibenzo-p-dioxin, in mouse psoriasis skin [ 111 ]. Galangin, an active flavonoid extracted from Alpinia officinarum , Alpina galanga , and propolis, downregulated the NF-κB signaling pathway in mouse psoriatic skin [ 112 ].…”

Section: Nrf2 and Psoriasismentioning

confidence: 99%

The Role of KEAP1-NRF2 System in Atopic Dermatitis and Psoriasis

Ogawa

Ishitsuka

2022

Antioxidants

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The Kelch-like erythroid cell-derived protein with cap‘n’collar homology-associated protein 1 (KEAP1)-nuclear factor erythroid-2-related factor 2 (NRF2) system, a thiol-based sensor-effector apparatus, exerts antioxidative and anti-inflammatory effects and maintains skin homeostasis. Thus, NRF2 activation appears to be a promising treatment option for various skin diseases. However, NRF2-mediated defense responses may deteriorate skin inflammation in a context-dependent manner. Atopic dermatitis (AD) and psoriasis are two common chronic inflammatory skin diseases caused by a defective skin barrier, dysregulated immune responses, genetic predispositions, and environmental factors. This review focuses on the role of the KEAP1-NRF2 system in the pathophysiology of AD and psoriasis and the therapeutic approaches that utilize this system.

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Rapamycin Alleviates 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Aggravated Dermatitis in Mice with Imiquimod-Induced Psoriasis-Like Dermatitis by Inducing Autophagy

Cited by 22 publications

References 61 publications

Dissecting the Crosstalk Between Nrf2 and NF-κB Response Pathways in Drug-Induced Toxicity

Dissecting the Crosstalk Between Nrf2 and NF-κB Response Pathways in Drug-Induced Toxicity

Aryl hydrocarbon receptor (AhR) reveals evidence of antagonistic pleiotropy in the regulation of the aging process

The Role of KEAP1-NRF2 System in Atopic Dermatitis and Psoriasis

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