Tranexamic acid improves psoriasis-like skin inflammation: Evidence from in vivo and in vitro studies

Biomed Pharmacother. 2023 Oct:166:115307. doi: 10.1016/j.biopha.2023.115307. Epub 2023 Aug 11.

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.

Keywords: Autophagy; IL-17; Imiquimod; NLRP3; Psoriasis; Tranexamic acid.

MeSH terms

  • Animals
  • Dermatitis*
  • Disease Models, Animal
  • Humans
  • Imiquimod / pharmacology
  • Inflammasomes
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Interleukin-17 / metabolism
  • Keratin-17
  • Keratinocytes
  • Mice
  • Mice, Inbred BALB C
  • NF-E2-Related Factor 2
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Psoriasis* / chemically induced
  • Psoriasis* / drug therapy
  • Psoriasis* / metabolism
  • Skin
  • Tranexamic Acid* / pharmacology
  • Tranexamic Acid* / therapeutic use

Substances

  • Interleukin-17
  • Tranexamic Acid
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Keratin-17
  • NF-E2-Related Factor 2
  • Imiquimod
  • NF-kappa B