Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation

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

doi:10.3390/ijms21062195

Cited by 42 publications

(39 citation statements)

References 40 publications

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“…Rapamycin downregulated AHR expression and increased autophagy-related factor expression in IMQ-induced psoriatic mouse skin. We previously demonstrated that the AHR agonist TCDD induced inflammation through autophagy inhibition using an in vitro psoriasis keratinocyte model and ex vivo psoriatic skin tissue study, and these findings are consistent with those noted in this study [ 31 ].…”

Section: Discussionsupporting

confidence: 92%

“…Abuse of alcohol, cannabis, and tobacco affects the treatment response of biologics in psoriasis [ 32 ]. Evidence regarding the effects of the environmental contaminant TCDD via AHR activation on the pathogenesis of psoriasis has accumulated [ 31 , 33 ]. AHR is a ligand-dependent transcription factor that plays a key physiological role in the maintenance of homeostasis in various organs and tissues and also influences pathological xenobiotic toxic effects [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have indicated that autophagy dysfunction in keratinocytes is involved in psoriatic inflammation [ 26 , 39 ]. We previously indicated that AHR activation via TCDD suppressed keratinocyte autophagy, inducing psoriatic inflammation in in vitro and ex vivo studies [ 31 ]. The present study demonstrated that in an IMQ-induced psoriatic mouse model, AHR activation through TCDD inhibited autophagy-related factor expression in lesional skin and subsequently aggravated skin inflammation clinically as well as molecular changes.…”

Section: Discussionmentioning

confidence: 99%

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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

Kim

Kang

et al. 2021

IJMS

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Recently, the mTOR signaling has emerged as an important player in the pathogenesis of psoriasis. We previously found that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced psoriatic skin inflammation was related to the inhibition of autophagy in keratinocytes. However, the effects and detailed molecular mechanisms of the mTOR inhibitor rapamycin and TCDD on psoriasis in vivo remain to be elucidated. In this study, we aimed to evaluate the effects of rapamycin and TCDD on skin lesions in imiquimod (IMQ)-induced psoriasis using a mouse model. TCDD aggravated skin inflammation in an IMQ-induced psoriatic mouse model. Furthermore, TCDD increased the expression of aryl hydrocarbon receptor (AHR), CYP1A1, proinflammatory cytokines, oxidative stress markers (NADPH oxidase (Nox) 2, Nox4), and phosphorylated P65NF-ĸB, whereas the expression of autophagy-related factors and the antioxidant marker nuclear factor-erythroid 2-related factor 2 (NRF2) decreased. Rapamycin reduced the aggravated skin inflammation induced by TCDD and restored TCDD-induced autophagy suppression and the increase of AHR expression, oxidative stress, and inflammatory response in the skin lesions of a psoriatic mouse model. In conclusion, we demonstrated that rapamycin alleviates TCDD-induced aggravated dermatitis in mice with imiquimod-induced psoriasis-like dermatitis through AHR and autophagy modulation.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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

Kim

Kang

et al. 2021

IJMS

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“…In the degradation of damaged/modified proteins, the proteasomal system is supported by the process of autophagy, which degrades, among others, protein aggregates that have not undergone proteasomal proteolysis and may accumulate in cells [ 57 , 58 ]. Our findings indicate a significant increase in autophagy units in the blood cells of patients with psoriasis.…”

Section: Discussionmentioning

confidence: 99%

Reduced Proteasome Activity and Enhanced Autophagy in Blood Cells of Psoriatic Patients

Karabowicz

Wroński²,

Ostrowska

et al. 2020

IJMS

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Psoriasis is a skin disease that is accompanied by oxidative stress resulting in modification of cell components, including proteins. Therefore, we investigated the relationship between the intensity of oxidative stress and the expression and activity of the proteasomal system as well as autophagy, responsible for the degradation of oxidatively modified proteins in the blood cells of patients with psoriasis. Our results showed that the caspase-like, trypsin-like, and chymotrypsin-like activity of the 20S proteasome in lymphocytes, erythrocytes, and granulocytes was lower, while the expression of constitutive proteasome and immunoproteasome subunits in lymphocytes was increased cells of psoriatic patients compared to healthy subjects. Conversely, the expression of constitutive subunits in erythrocytes, and both constitutive and immunoproteasomal subunits in granulocytes were reduced. However, a significant increase in the autophagy flux (assessed using LC3BII/LC3BI ratio) independent of the AKT pathway was observed. The levels of 4-HNE, 4-HNE-protein adducts, and proteins carbonyl groups were significantly higher in the blood cells of psoriatic patients. The decreased activity of the 20S proteasome together with the increased autophagy and the significantly increased level of proteins carbonyl groups and 4-HNE-protein adducts indicate a proteostatic imbalance in the blood cells of patients with psoriasis.

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“…HaCaT cells are immortalized cells, which are commonly used in the studies relevant to psoriasis (13). To mimic conditions of psoriatic keratinocytes, HaCaT cells were induced with M5 (consisting of IL-17A, IL-22, IL-1alpha, TNF-alpha and Oncostatin M) as previous reported (27).…”

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confidence: 99%

Diagnostic value of miR-106a-5p in patients with psoriasis and its regulatory role in inflammatory responses

Miao

Tong

et al. 2020

Preprint

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Background: Psoriasis is a multifactorial, recurring, and chronic inflammatory skin disease. This study was designed to explore the potential role of microRNA-106a-5p (miR-106a-5p) in psoriasis.Methods: The expression levels of miR-106a-5p in the serum of psoriasis patients and healthy individuals were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic value of miR-106a-5p in serum was evaluated by the receiver operating characteristics curve (ROC). The levels of interleukin-22 (IL-22), interleukin-17A (IL-17A), and tumor necrosis factor-alpha (TNF-alpha) were determined by enzyme-linked immunosorbent assay.Results: The serum expression of miR-106a-5p was found to be up-regulated in psoriasis patients. ROC curve showed that miR-106a-5p had high specificity and sensitivity in the diagnosis of psoriasis. The correlation between the serum expression level of miR-106a-5p and PASI was positive. The relative expression levels of IL-17A, IL-22 and TNF-alpha in serum of psoriasis patients were significantly upregulated compared with that in healthy control, and showed positive association with serum miR-106a-5p levels. Cell experiments demonstrated that upregulation of miR-106a-5p could promote cell proliferation, and the levels of IL-22, IL-17A and TNF-alpha were upregulated significantly in M5-induced HaCaT cells.Conclusion: Considering the novel and vital role in psoriasis progression, miR-106a-5p is expected to be a new potent target for treatment of psoriasis. MiR-106-5p was expected to use for more immunity diseases research and therapy.

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Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation

Cited by 42 publications

References 40 publications

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

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

Reduced Proteasome Activity and Enhanced Autophagy in Blood Cells of Psoriatic Patients

Diagnostic value of miR-106a-5p in patients with psoriasis and its regulatory role in inflammatory responses

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