Table 2.
Factors that can modulate LL-37, hBD-2, hepcidin, and Lcn2 expression.
| LL-37 |
hBD-2 |
Hepcidin |
Lcn2 |
||||
|---|---|---|---|---|---|---|---|
| Factor upregulation | Reference | Factor upregulation | Reference | Factor upregulation | Reference | Factor upregulation | Reference |
| IL-17A (in synergy with vitamin D3) | (84) | LPS | (85) | IL-6, IL-1α, IL-22, oncostatin M | (86, 87) | Anemia | (88) |
| TNFα, IFNγ | (89, 90) | IL-1, TNFα | (91) | Activin B | (92) | LPS | (62) |
| Injury, wounding, UVB irradiation | (89, 93) | TLR-2 | (94, 95) | Liver metabolic activities | (96) | IL-1α and β, IL-4, IL-17, IL-22, IL-9, TNFα | (97–104) |
| Sodium butyrate, phenyl butyrate | (105–107) | IL-17 | (76) | Oxygenases | (96) | IGF-1, TGFα | (108) |
| TLR agonists, lithocholic acid, vitamin D receptor agonists | (89, 109–112) | AP-1, MEF | (94, 113) | Small molecule activators of Stat/Smad pathways (genistein) | (114) | Serum, growth factors, phorbol esters, Glucocorticoids (dexamethasone) | (115, 116) |
| ER stress | (93) | Neutrophil elastase | (117) | BMP6 | (118) | 3-cis retinoic acid (isotretinoin); 4-HPR | (119, 120) |
| Short-chain fatty acids, Zn2+, lactose | (121–123) | Calcium | (124) | TMPRSS6 siRNA or ASOs | (125) | MK886, nordihydroguaiaretic acid | (126, 127) |
| BCG | (128) | UV light | (89) | HFE, TfR2 | (96) | COX-2 inhibitors, celecoxib-derived PDK1 inhibitors | (126) |
| Factor downregulation | Reference | Factor downregulation | Reference | Factor downregulation | Reference | Factor downregulation | Reference |
| Bacterial exotoxins, Shigella, Neisseria infection | (107, 129–131) | Glucocorticoids (dexamethasone) | (76, 124) | Oxidative stress (ROS); hypoxia; heparin; anti-inflammatories (anti-IL-6/IL-6R (siltuximab)/(tocilizumab), anti-TNFα, AG490) | (96, 132–136) | l-Glutamine, N-acetylcysteine | (137, 138) |
| IL-6, IFNγ, calcipotriol | (89, 139) | Calcium quelator | (124) | Matriptase2, s-HJV-Fc, GDF15, erythropoiesis-stimulating agents | (96, 132, 140) | Paricalcitol | (141) |
| Psychological stress; transmigration across activated endothelium | (142, 143) | Inhibitors of NF-κB and AP-1 | (124) | Small molecule inhibitors of the BMPR type I kinase (LDN-193189); anti-BMP6 antibody; HJV ASOs, hepcidin ASOs or siRNA, TfR2 siRNA; PpYLKTK (disruptor of STAT3 dimerization) | (118, 140, 183–187) | EGF, miR-138 | (144, 145) |
IL-17A, interleukin-17; TNF, tumor necrosis alpha; IFN, interferon; UV, ultraviolet light; IL-6, interleukin 6; LPS, lipopolysaccharide; IL-1, interleukin 1; IL-22, interleukin 22; TLR, toll-like receptor; BCG, Mycobacterium bovis bacillus Calmette–Guérin; AP-1, activator protein 1; MEF, myeloid elf-1-like factor; NF-κB, nuclear factor-κB; BMP6, bone morphogenetic protein 6; TMPRSS6, transmembrane protease serine 6; siRNA, small interfering RNA; HFE, human hemochromatosis protein; TfR2, transferrin receptor 2; s-HJV-Fc, soluble form of hemojuvelin; GDF15, growth differentiation factor 15; BMPR, bone morphogenetic protein receptor; STAT3, signal transducer and activator of transcription 3; ASOs, antisense oligonucleotides; HJV, hemojuvelin; EGF, epidermal growth factor; COX-2, cyclooxygenase-2; PDK1, phosphoinositide-dependent kinase 1; 4-HPR; N-(4-hydroxyphenyl)retinamide; ER, endoplasmic reticulum; miR-138, microRNA-138; IGF-1, insulin like growth factor-1; TGFα, transforming growth factor alpha.