Mutated IL-32θ (A94V) inhibits COX2, GM-CSF and CYP1A1 through AhR/ARNT and MAPKs/NF-κB/AP-1 in keratinocytes exposed to PM10

• Published in: Scientific reports Vol. 15; no. 1; pp. 1994 - 13
• Main Authors: Kim, Jinju, Lim, Chae-Min, Kim, Nahyun, Kim, Hong-Gyum, Hong, Jin-Tae, Yang, Young, Yoon, Do-Young
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.01.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/250/127; 631/250/256; 692/699/4033; Cancer; Cardiovascular diseases; Cyclooxygenase-2; Cytochrome P450; Fine dust; Granulocyte-macrophage colony-stimulating factor; HaCaT; Humanities and Social Sciences; Inflammation; Isoforms; Keratinocytes; MAPK; multidisciplinary; NF-κB protein; Nuclear transport; PAH; Particulate matter; PM10; Science; Science (multidisciplinary); Signal transduction; Skin; Skin inflammation; Transcription factors; Translocation; Fine dust; Skin inflammation; one-point mutated IL-32θ (A94V); PAH; MAPK; PM; HaCaT
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-83159-z

Exposure to particulate matter (PM) in the air harms human health. Most studies on particulate matter’s (PM) effects have primarily focused on respiratory and cardiovascular diseases. Recently, IL-32θ, one of the IL-32 isoforms, has been demonstrated to modulate cancer development and inflammatory responses. This study revealed that one-point mutated IL-32θ (A94V) plays an important role in attenuating skin inflammation. IL-32θ (A94V) inhibited PM-induced COX-2, a pro-inflammatory cytokine GM-CSF and CYP1A1 in PM-exposed human keratinocytes HaCaT cells. IL-32θ (A94V) modulating effects were mediated via down-regulating ERK/p38/NF-κB/ AP-1 and AhR/ARNT signaling pathways. Our study indicates that PM triggers skin inflammation by upregulating COX-2, GM-CSF and CYP1A1 expression. IL-32θ (A94V) suppresses the expressions of COX-2, GM-CSF, and CYP1A1 by blocking the nuclear translocation of NF-κB and AP-1, as well as inhibiting the activation of the AhR/ARNT signaling pathway. Our findings offer valuable insights into developing therapeutic strategies and potential drugs to mitigate PM-induced skin inflammation by inhibiting the ERK/p38/NF-κB/AP-1 and AhR/ARNT signaling pathways.