Article ; Online: Tranexamic acid improves psoriasis-like skin inflammation: Evidence from in vivo and in vitro studies.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
2023 Volume 166, Page(s) 115307
Abstract: The chronic disease psoriasis is associated with severe inflammation and abnormal keratinocyte propagation in the skin. Tranexamic acid (TXA), a plasmin inhibitor, is used to cure serious bleeding. We investigated whether TXA ointment mitigated Imiquimod ...
| Abstract | The chronic disease psoriasis is associated with severe inflammation and abnormal keratinocyte propagation in the skin. Tranexamic acid (TXA), a plasmin inhibitor, is used to cure serious bleeding. We investigated whether TXA ointment mitigated Imiquimod (IMQ)-induced psoriasis-like inflammation. Furthermore, this study investigated the effect of noncytotoxic concentrations of TXA on IL-17-induced human keratinocyte (HaCaT) cells to determine the status of proliferative psoriatic keratinocytes. We found that TXA reduced IMQ-induced psoriasis-like erythema, thickness, scaling, and cumulative scores (erythema plus thickness plus scaling) on the back skin of BALB/c mice. Additionally, TXA decreased ear thickness and suppressed hyperkeratosis, hyperplasia, and inflammation of the ear epidermis in IMQ-induced BALB/c mice. Furthermore, TXA inhibited IMQ-induced splenomegaly in BALB/c mouse models. In IL-17-induced HaCaT cells, TXA inhibited ROS production and IL-8 secretion. Interestingly, TXA suppressed the IL-17-induced NFκB signaling pathway via IKK-mediated IκB degradation. TXA inhibited IL-17-induced activation of the NLRP3 inflammasome through caspase-1 and IL1β expression. TXA inhibited IL-17-induced NLRP3 inflammasome activation by enhancing autophagy, as indicated by LC3-II accumulation, p62/SQSTM1 expression, ATG4B inhibition, and Beclin-1/Bcl-2 dysregulation. Notably, TXA suppressed IL-17-induced Nrf2-mediated keratin 17 expression. N-acetylcysteine pretreatment reversed the effects of TXA on NFκB, NLRP3 inflammasomes, and the Nrf2-mediated keratin 17 pathway in IL-17-induced HaCaT cells. Results further confirmed that in the ear skin of IMQ-induced mice, psoriasis biomarkers such as NLRP3, IL1β, Nrf2, and keratin 17 expression were downregulated by TXA treatment. TXA improves IMQ-induced psoriasis-like inflammation in vivo and psoriatic keratinocytes in vitro. Tranexamic acid is a promising future treatment for psoriasis. |
|---|---|
| MeSH term(s) | Humans ; Animals ; Mice ; Interleukin-17/metabolism ; Tranexamic Acid/pharmacology ; Tranexamic Acid/therapeutic use ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Keratin-17 ; NF-E2-Related Factor 2 ; Psoriasis/chemically induced ; Psoriasis/drug therapy ; Psoriasis/metabolism ; Dermatitis ; Skin ; Keratinocytes ; Inflammation/drug therapy ; Inflammation/chemically induced ; Imiquimod/pharmacology ; NF-kappa B/metabolism ; Mice, Inbred BALB C ; Disease Models, Animal |
| Chemical Substances | Interleukin-17 ; Tranexamic Acid (6T84R30KC1) ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Keratin-17 ; NF-E2-Related Factor 2 ; Imiquimod (P1QW714R7M) ; NF-kappa B |
| Language | English |
| Publishing date | 2023-08-11 |
| Publishing country | France |
| Document type | Journal Article |
| ZDB-ID | 392415-4 |
| ISSN | 1950-6007 ; 0753-3322 ; 0300-0893 |
| ISSN (online) | 1950-6007 |
| ISSN | 0753-3322 ; 0300-0893 |
| DOI | 10.1016/j.biopha.2023.115307 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Ud II Zs.198: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.