Anti-Inflammasome Effect of Impressic Acid on Diesel Exhaust Particulate Matter-Induced NLRP1 Inflammasome via the Keap1/p62/Nrf2-Signaling Pathway in Keratinocytes
Diesel exhaust particulate (DEP) is widely recognized to weaken lung function and skin diseases. When the skin, which defends against external factors, is exposed to PM2.5, various chronic inflammatory diseases occur. When keratinocytes recognize harmful signals, they synthesize the NOD-like recepto...
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MDPI AG
2025-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/5/610 |
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| author | Seung Yeon Lee Gi Ho Lee Jeonghwan Maeng Su Yeon Kim Hwi-Yeol Yun Gil-Saeng Jeong Hye Gwang Jeong |
| author_facet | Seung Yeon Lee Gi Ho Lee Jeonghwan Maeng Su Yeon Kim Hwi-Yeol Yun Gil-Saeng Jeong Hye Gwang Jeong |
| author_sort | Seung Yeon Lee |
| collection | DOAJ |
| description | Diesel exhaust particulate (DEP) is widely recognized to weaken lung function and skin diseases. When the skin, which defends against external factors, is exposed to PM2.5, various chronic inflammatory diseases occur. When keratinocytes recognize harmful signals, they synthesize the NOD-like receptor protein 1 (NLRP1) inflammasome. DEP enhances NF-κB signaling and NLRP1 inflammasome expression through the interaction of TXNIP with NLRP1 in keratinocytes. Although many studies have reported the anti-inflammatory and antioxidant characteristics of Impressic acid (IPA), the umbrella consequences of IPA for PM2.5-influenced inflammasomes and the associated mechanisms remain unknown. Therefore, this study aimed to examine the protective function of IPA against inflammation in human keratinocytes. IPA attenuated the NLRP1 expression, caspase-1, IL-1β actuation, and NF-κB and IκB phosphorylation induction by DEP. IPA upregulated the Nrf2, HO-1, and NQO1 expression through CaMKKβ, AMPK, and GSK3β phosphorylation. Also, IPA led to the elevation of p62 and the degradation of the Keap1 protein. ML385 reversed the suppressive effect of IPA on the NLRP1 inflammasome, which was enhanced by DEP, and NAC counteracted the effect of ML385. These findings indicate that IPA can suppress inflammation induced by PM2.5 by expressing antioxidant enzymes through the Keap1/p62/Nrf2-signaling pathway in human keratinocytes. |
| format | Article |
| id | doaj-art-04da0a9ca69e466f9d97b4a89a42478d |
| institution | DOAJ |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-04da0a9ca69e466f9d97b4a89a42478d2025-08-20T03:14:39ZengMDPI AGAntioxidants2076-39212025-05-0114561010.3390/antiox14050610Anti-Inflammasome Effect of Impressic Acid on Diesel Exhaust Particulate Matter-Induced NLRP1 Inflammasome via the Keap1/p62/Nrf2-Signaling Pathway in KeratinocytesSeung Yeon Lee0Gi Ho Lee1Jeonghwan Maeng2Su Yeon Kim3Hwi-Yeol Yun4Gil-Saeng Jeong5Hye Gwang Jeong6College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaDiesel exhaust particulate (DEP) is widely recognized to weaken lung function and skin diseases. When the skin, which defends against external factors, is exposed to PM2.5, various chronic inflammatory diseases occur. When keratinocytes recognize harmful signals, they synthesize the NOD-like receptor protein 1 (NLRP1) inflammasome. DEP enhances NF-κB signaling and NLRP1 inflammasome expression through the interaction of TXNIP with NLRP1 in keratinocytes. Although many studies have reported the anti-inflammatory and antioxidant characteristics of Impressic acid (IPA), the umbrella consequences of IPA for PM2.5-influenced inflammasomes and the associated mechanisms remain unknown. Therefore, this study aimed to examine the protective function of IPA against inflammation in human keratinocytes. IPA attenuated the NLRP1 expression, caspase-1, IL-1β actuation, and NF-κB and IκB phosphorylation induction by DEP. IPA upregulated the Nrf2, HO-1, and NQO1 expression through CaMKKβ, AMPK, and GSK3β phosphorylation. Also, IPA led to the elevation of p62 and the degradation of the Keap1 protein. ML385 reversed the suppressive effect of IPA on the NLRP1 inflammasome, which was enhanced by DEP, and NAC counteracted the effect of ML385. These findings indicate that IPA can suppress inflammation induced by PM2.5 by expressing antioxidant enzymes through the Keap1/p62/Nrf2-signaling pathway in human keratinocytes.https://www.mdpi.com/2076-3921/14/5/610diesel exhaust particlesNLRP1 inflammasomeimpressic acidNrf2keratinocytes |
| spellingShingle | Seung Yeon Lee Gi Ho Lee Jeonghwan Maeng Su Yeon Kim Hwi-Yeol Yun Gil-Saeng Jeong Hye Gwang Jeong Anti-Inflammasome Effect of Impressic Acid on Diesel Exhaust Particulate Matter-Induced NLRP1 Inflammasome via the Keap1/p62/Nrf2-Signaling Pathway in Keratinocytes Antioxidants diesel exhaust particles NLRP1 inflammasome impressic acid Nrf2 keratinocytes |
| title | Anti-Inflammasome Effect of Impressic Acid on Diesel Exhaust Particulate Matter-Induced NLRP1 Inflammasome via the Keap1/p62/Nrf2-Signaling Pathway in Keratinocytes |
| title_full | Anti-Inflammasome Effect of Impressic Acid on Diesel Exhaust Particulate Matter-Induced NLRP1 Inflammasome via the Keap1/p62/Nrf2-Signaling Pathway in Keratinocytes |
| title_fullStr | Anti-Inflammasome Effect of Impressic Acid on Diesel Exhaust Particulate Matter-Induced NLRP1 Inflammasome via the Keap1/p62/Nrf2-Signaling Pathway in Keratinocytes |
| title_full_unstemmed | Anti-Inflammasome Effect of Impressic Acid on Diesel Exhaust Particulate Matter-Induced NLRP1 Inflammasome via the Keap1/p62/Nrf2-Signaling Pathway in Keratinocytes |
| title_short | Anti-Inflammasome Effect of Impressic Acid on Diesel Exhaust Particulate Matter-Induced NLRP1 Inflammasome via the Keap1/p62/Nrf2-Signaling Pathway in Keratinocytes |
| title_sort | anti inflammasome effect of impressic acid on diesel exhaust particulate matter induced nlrp1 inflammasome via the keap1 p62 nrf2 signaling pathway in keratinocytes |
| topic | diesel exhaust particles NLRP1 inflammasome impressic acid Nrf2 keratinocytes |
| url | https://www.mdpi.com/2076-3921/14/5/610 |
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