Table 2.
LOX regulation in inflammatory pathways.
| Inflammatory Mediators | Regulatory Activity | Signaling Pathways Involved | Refs. |
|---|---|---|---|
| TNF-α | LOX inhibition in chronic inflammation | TNF-α downregulation via Vegf and Fak (mouse model); miR203-mediated silencing (mesenchymal cells); TNF-α receptor and protein kinase C activation-mediated (endothelial cells) | [59,60,61] |
| LOX upregulation | TGF-β/PI3K signaling (myocardial fibrosis); NF-κB/TGF-β-mediated signaling (fibroblast-epithelial interactions, esophagitis) |
[38,62] | |
| IL-1β | Induced/inhibited LOX expression | Overexpression via ERK1/2/JNK and c-JUN activation (rat granulosa cells); inhibition by p38 and ERK1/2, NF-κB activation and interaction with GATA3 at the NF-κB binding LOX promoter site (amnion); via IL-1β-activated NF-κβ (aortic smooth muscle cells); IL-1β-mediated inhibition (ligaments) | [63,64,65,66] |
| IL-4 | Pro-/anti-inflammatory activity-related upregulation of LOX | SATA6, PI3K, p38MAPK (ovarian epithelium) | [68] |
| IL-6 | Epigenetic control of LOX expression | Downregulation through JAK2, Fli1 and Dnmt1 (osteoblasts) | [69] |
| IFN-γ | Pro-inflammatory control of LOX | Downregulation by transcription and mRNA half-life control (aortic smooth muscle cells, cardiac fibroblast) | [71,72] |
TNF: tumor necrosis factor; IL: interleukin; IFN: interferon; VEGF: vascular endothelial growth factor; TGF-β: transforming growth factor beta; PI3K: phosphoinositide 3-kinase; ERK: extracellular signal-regulated kinase; JNK: Jun N-terminal kinase; p38MAPK: P38 mitogen-activated protein kinase; NF-κB: Nuclear Factor kappa B; PI3K: phosphatidylinositol-3-kinase FAK: focal adhesion kinase; JAK: Janus kinase; : Flil: Flagellar protein; Dnmt1: DNA (cytosine-5)-methyltransferase 1; LOX: lysyl oxidase.