Ultraviolet Radiation‐Induced Downregulation of SERCA2 Mediates Activation of NLRP3 Inflammasome in Basal Cell Carcinoma

Ahmad, Israr; Muneer, Kashiff M.; Chang, Michelle E.; Nasr, Hana M.; Clay, Jacqueline M.; Huang, Conway C.; Yusuf, Nabiha

doi:10.1111/php.12725

Cited by 24 publications

(15 citation statements)

References 50 publications

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“…It has been well documented that inflammasome can be activated by several factors, among them UVB exposure [8]. In the present study, we demonstrated that UVB irradiation led to up-regulation of NLRP3, ASC and caspase-1 expression and, consequently, promoted a significant increase in IL-1β production in comparison with non-exposed cells (Figure 3A–D).…”

Section: Resultssupporting

confidence: 70%

“…Moreover, NLRP3 inflammasome activation by UVB increases not only IL-1β but also other pro-inflammatory cytokines such as IL-1α, IL-6, TNF-α or the mediator PGE2 [7]. In this line, NLRP3 inflammasome plays an important role in UVB-induced skin inflammatory responses and has a critical function in skin pathologies initiation such as cancer [8]. In addition, the inflammasome adaptor protein ASC has shown anti-tumour activity by activation of tumour suppressor protein p53 in UVB-irradiated keratinocytes [39].…”

Section: Discussionmentioning

confidence: 99%

“…NLRP3 gen induction results in activation of caspase-1, which by cleavage catalyses the processing of pro-IL-1β in cytosol to mature form, leading to IL-1β production in the extracellular medium [7]. In the last years, some authors have demonstrated the implication of NLRP3 inflammasome in tumorigenesis and cancer development, specifically in basal cell carcinomas [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Fucoxanthin and Rosmarinic Acid Combination Has Anti-Inflammatory Effects through Regulation of NLRP3 Inflammasome in UVB-Exposed HaCaT Keratinocytes

et al. 2019

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Excessive exposure to ultraviolet (UV) radiation is the main risk factor to develop skin pathologies or cancer because it encourages oxidative condition and skin inflammation. In this sense, strategies for its prevention are currently being evaluated. Natural products such as carotenoids or polyphenols, which are abundant in the marine environment, have been used in the prevention of oxidative stress due to their demonstrated antioxidant activities. Nevertheless, the anti-inflammatory activity and its implication in photo-prevention have not been extensively studied. Thus, we aimed to evaluate the combination of fucoxanthin (FX) and rosmarinic acid (RA) on cell viability, apoptosis induction, inflammasome regulation, and anti-oxidative response activation in UVB-irradiated HaCaT keratinocytes. We demonstrated for the first time that the combination of FX and RA (5 µM RA plus 5 μM FX, designated as M2) improved antioxidant and anti-inflammatory profiles in comparison to compounds assayed individually, by reducing UVB-induced apoptosis and the consequent ROS production. Furthermore, the M2 combination modulated the inflammatory response through down-regulation of inflammasome components such as NLRP3, ASC, and Caspase-1, and the interleukin (IL)-1β production. In addition, Nrf2 and HO-1 antioxidant genes expression increased in UVB-exposed HaCaT cells pre-treated with M2. These results suggest that this combination of natural products exerts photo-protective effects by down-regulating NRLP3-inflammasome and increasing Nrf2 signalling pathway.

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Section: Resultssupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fucoxanthin and Rosmarinic Acid Combination Has Anti-Inflammatory Effects through Regulation of NLRP3 Inflammasome in UVB-Exposed HaCaT Keratinocytes

et al. 2019

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“…8-OH-dG levels correlate with disease severity index [ 8 ]. Moreover, NLRP3 has been reported as an important player in the initiation and promotion of nonmelanoma skin cancers that are commonly characterized by 8-OH-dG lesions [ 95 , 96 ]. UV radiations induce the increase of 8-OH-dG lesions and inflammatory responses through increased ROS production in human keratinocytes [ 97 , 98 ].…”

Section: Discussionmentioning

confidence: 99%

miR‐200a Modulates the Expression of the DNA Repair Protein OGG1 Playing a Role in Aging of Primary Human Keratinocytes

Tinaburri

D’Errico

Sileno

et al. 2018

Oxidative Medicine and Cellular Longevity

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Oxidative DNA damage accumulation may induce cellular senescence. Notably, senescent cells accumulate in aged tissues and are present at the sites of age-related pathologies. Although the signaling of DNA strand breaks has been extensively studied, the role of oxidative base lesions has not fully investigated in primary human keratinocyte aging. In this study, we show that primary human keratinocytes from elderly donors are characterized by a significant accumulation of the oxidative base lesion 8-OH-dG, impairment of oxidative DNA repair, and increase of miR-200a levels. Notably, OGG1-2a, a critical enzyme for 8-OH-dG repair, is a direct target of miR-200a and its expression levels significantly decrease in aged keratinocytes. The 8-OH-dG accumulation displays a significant linear relationship with the aging biomarker p16 expression during keratinocyte senescence. Interestingly, we found that miR-200a overexpression down-modulates its putative target Bmi-1, a well-known p16 repressor, and up-regulates p16 itself. miR-200a overexpression also up-regulates the NLRP3 inflammasome and IL-1β expression. Of note, primary keratinocytes from elderly donors are characterized by NRPL3 activation and IL-1β secretion. These findings point to miR-200a as key player in primary human keratinocyte aging since it is able to reduce oxidative DNA repair activity and may induce several senescence features through p16 and IL-1β up-regulation.

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“…Nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflamma-some upregulation at the expression or activation level has been reported to play an important role in radiation damage including RISRs in recent years 18–20. NLRP3 inflammasome is a multi-protein complex that activates caspase-1, which leads to the maturation of the pro-inflammatory cytokines IL-1β and IL-18 21…”

Section: Mechanism Of Risrsmentioning

confidence: 99%

Radiation-induced skin reactions: mechanism and treatment

Wei¹,

Meng²,

Hou³

et al. 2018

CMAR

142

109

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Radiotherapy (RT) is a major treatment for malignant tumors. The latest data show that >70% of patients with malignant tumors need RT at different periods. Skin changes can be experienced by up to 95% of patients who underwent RT. Inflammation and oxidative stress (OS) have been shown to be generally associated with radiation-induced skin reactions (RISRs). Inflammatory response and OS interact and promote each other during RISRs. Severe skin reactions often have a great impact on the progress of RT. The treatment of RISRs is particularly critical because advanced RT technology can also lead to skin reactions. RISRs are classified into acute and chronic reactions. The treatment methods for acute RISRs include steroid treatment, creams, ointments, and hydrocolloid dressings, depending on the reaction grading. Chronic RISRs includes chronic ulcerations, telangiectasias, and fibrosis of the skin, and advanced treatments such as mesenchymal stem cells, hyperbaric oxygen therapy, superoxide dismutase, and low-intensity laser therapy can be considered. Here, we review and summarize the important mechanisms that cause RISRs as well as the standard and advanced treatments for RISRs.

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Ultraviolet Radiation‐Induced Downregulation of SERCA2 Mediates Activation of NLRP3 Inflammasome in Basal Cell Carcinoma

Cited by 24 publications

References 50 publications

Fucoxanthin and Rosmarinic Acid Combination Has Anti-Inflammatory Effects through Regulation of NLRP3 Inflammasome in UVB-Exposed HaCaT Keratinocytes

Fucoxanthin and Rosmarinic Acid Combination Has Anti-Inflammatory Effects through Regulation of NLRP3 Inflammasome in UVB-Exposed HaCaT Keratinocytes

miR‐200a Modulates the Expression of the DNA Repair Protein OGG1 Playing a Role in Aging of Primary Human Keratinocytes

Radiation-induced skin reactions: mechanism and treatment

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