Nitrogen mustard prevents transport of Fra-1 into the nucleus to promote c-Fos- and FosB-dependent IL-8 induction in injured mouse epidermis

Ye, Feng; Zeng, Qinya; Dan, Guorong; Dong, Xunhu; Chen, Mingliang; Sai, Yan; Lin, Hai; Zou, Zhongmin

doi:10.1016/j.toxlet.2019.10.006

Cited by 9 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…25 Recently, our group showed that NM prevent fos-related antigen-1 from entering into the nucleus, which leads to IL-8 overexpression and contributes to NM-induced cutaneous inflammation. 20 Antiinflammatory agents targeting these related signaling pathways have been widely explored for the treatment of vesicant-caused dermal toxicity. 26 However, effective targeted therapies are still inadequate, suggesting the involvement of other specific mechanisms in vesicant-induced cutaneous inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…After 48 h, a circular area of 0.5 cm 2 on the dorsal-lumbar region of the animal and centered on the body axis, where mice were not able to perturb, was chosen for NM exposure in a fume hood as reported previously. 20 And dorsal skin of mice (n = 6/group) was topically exposed to NM (3.2 mg/200 μL acetone), whereas control mice received 200 μL acetone only, as described earlier. 21 VD3 was reconstituted in DMSO and diluted in mineral oil for intraperitoneal injection at a concentration of 50 ng/ 100 μL per mouse combined with or without anakinra (50 mg/kg), at 1 h before NM exposure.…”

Section: Animal Treatmentsmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin D3 ameliorates nitrogen mustard‐induced cutaneous inflammation by inactivating the NLRP3 inflammasome through the SIRT3–SOD2–mtROS signaling pathway

Dong

Feng

et al. 2021

Clinical & Translational Med

Self Cite

View full text Add to dashboard Cite

Nitrogen mustard (NM) causes severe skin injury with an obvious inflammatory response, which is lack of effective and targeted therapies. Vitamin D3 (VD3) has excellent anti‐inflammatory properties and is considered as a potential candidate for the treatment of NM‐induced dermal toxicity; however, the underlying mechanisms are currently unclear. Cyclooxygenase‐2 (COX2; a widely used marker of skin inflammation) plays a key role in NM‐induced cutaneous inflammation. Herein, we initially confirmed that NM markedly promoted COX2 expression in vitro and in vivo. NM also increased NOD‐like receptor family pyrin domain containing 3 (NLRP3) expression, caspase‐1 activity, and interleukin‐1β (IL‐1β) release. Notably, treatment with a caspase‐1 inhibitor (zYVAD‐fmk), NLRP3 inhibitor (MCC950), and NLRP3 or caspase‐1 siRNA attenuated NM‐induced NLRP3 inflammasome activation, with subsequent suppression of COX2 expression and IL‐1β release in keratinocytes. Meanwhile, NM increased mitochondrial reactive oxygen species (mtROS) and decreased manganese superoxide dismutase 2 (SOD2) and sirtuin 3 (SIRT3) activities. Mito‐TEMPO (a mtROS scavenger) ameliorated NM‐caused NLRP3 inflammasome activation in keratinocytes. Moreover, VD3 improved SIRT3 and SOD2 activities, decreased mtROS contents, inactivated the NLRP3 inflammasome, and attenuated cutaneous inflammation induced by NM in vitro and in vivo. The beneficial activity of VD3 against NM‐triggered cutaneous inflammation was enhanced by the inhibitors of IL‐1, mtROS, NLRP3, caspase‐1, and NLRP3 or caspase‐1 siRNAs, which was abolished in SIRT3 inhibitor or SIRT3 siRNA‐treated keratinocytes and skins from SIRT3−/− mice. In conclusion, VD3 ameliorated NM‐induced cutaneous inflammation by inactivating the NLRP3 inflammasome, which was partially mediated through the SIRT3–SOD2–mtROS signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Animal Treatmentsmentioning

confidence: 99%

Vitamin D3 ameliorates nitrogen mustard‐induced cutaneous inflammation by inactivating the NLRP3 inflammasome through the SIRT3–SOD2–mtROS signaling pathway

Dong

Feng

et al. 2021

Clinical & Translational Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…Notably, oxidative stress is considered an underlying causative factor of neurodegenerative diseases [58]. NF-κB, c-Fos, and FosB are required for the transcription of inflammatory cytokines, such as ILs, and induce an inflammatory response [59,60]. During inflammatory reactions, NF-κB and FosB are positively correlated, whereas superoxide dismutase (SOD) and glutathione peroxidase (GPx) elicit opposite outcomes [57].…”

Section: Cocainementioning

confidence: 99%

Cellular messenger molecules mediating addictive drug-induced cognitive impairment: cannabinoids, ketamine, methamphetamine, and cocaine

Sim

Kim

2022

Futur J Pharm Sci

View full text Add to dashboard Cite

Background Cognitive impairment is a commonly reported symptom with increasing life spans. Numerous studies have focused on identifying precise targets to relieve or reduce cognitive impairment; however, its underlying mechanism remains elusive. Most patients or animals exposed to addictive drugs exhibit cognitive impairment. Accordingly, the present review discusses the molecular changes induced by addictive drugs to clarify potential mechanisms that mediate cognitive impairments. Main body We investigated changes in cognitive function using four drugs: cannabinoids, ketamine, methamphetamine, and cocaine. Chronic administration of most addictive drugs reduces overall cognitive functions, such as working, spatial, and long-term recognition memories. Levels of several transcription factors involved in neuronal differentiation, as well as functional components of neurotransmitter receptors in neuronal cells, are reportedly altered. In addition, inflammatory factors showed a generally increasing trend. These impairments could be mediated by neuroinflammation, synaptic activity, and neuronal plasticity. Conclusion This review outlines the effects of acute or chronic drug use and potential molecular alterations in the central nervous system. In the central nervous system, addictive drug-induced changes in molecular pathways associated with cognitive function might play a pivotal role in elucidating the pathogenesis of cognitive impairment.

show abstract

“…Then, whether Fra-1 must be incorporated into the nucleus through transcription factors with other proteins to function. The activation of ERK by Nitrogen mustard (NM) increases Fra-1 levels in mouse epidermis and cultured human keratinocytes, where Fra-1 is mainly expressed in the cytoplasm rather than the nucleus, which contributes to IL-8 expression in NM-damaged skin ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the role of Fra-1 is related to its cellular localization. Fra-1 trapped in the cytoplasm inhibits Type I interferon responses to Malaria and Viral infections ( 22 ), also might be a driving force for IL-8 overexpression ( 23 ). Therefore, a comprehensive identification of the role of Fra-1 in immune processes may help to delineate new ways to ameliorate immune-related diseases such as infections, cancer, and cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

The Fra-1: Novel role in regulating extensive immune cell states and affecting inflammatory diseases

Zhou

Chen

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Fra-1(Fos-related antigen1), a member of transcription factor activator protein (AP-1), plays an important role in cell proliferation, apoptosis, differentiation, inflammation, oncogenesis and tumor metastasis. Accumulating evidence suggest that the malignancy and invasive ability of tumors can be significantly changed by directly targeting Fra-1. Besides, the effects of Fra-1 are gradually revealed in immune and inflammatory settings, such as arthritis, pneumonia, psoriasis and cardiovascular disease. These regulatory mechanisms that orchestrate immune and non-immune cells underlie Fra-1 as a potential therapeutic target for a variety of human diseases. In this review, we focus on the current knowledge of Fra-1 in immune system, highlighting its unique importance in regulating tissue homeostasis. In addition, we also discuss the possible critical intervention strategy in diseases, which also outline future research and development avenues.

show abstract

Nitrogen mustard prevents transport of Fra-1 into the nucleus to promote c-Fos- and FosB-dependent IL-8 induction in injured mouse epidermis

Cited by 9 publications

References 33 publications

Vitamin D3 ameliorates nitrogen mustard‐induced cutaneous inflammation by inactivating the NLRP3 inflammasome through the SIRT3–SOD2–mtROS signaling pathway

Vitamin D3 ameliorates nitrogen mustard‐induced cutaneous inflammation by inactivating the NLRP3 inflammasome through the SIRT3–SOD2–mtROS signaling pathway

Cellular messenger molecules mediating addictive drug-induced cognitive impairment: cannabinoids, ketamine, methamphetamine, and cocaine

The Fra-1: Novel role in regulating extensive immune cell states and affecting inflammatory diseases

Contact Info

Product

Resources

About