IL-20 Gene Expression Is Induced by IL-1β through Mitogen-Activated Protein Kinase and NF-κB-Dependent Mechanisms

Otkjaer, Kristian; Kragballe, Knud; Johansen, Claus; Funding, Anne Toftegaard; Just, Helle; Jensen, Uffe Birk; Sørensen, Lotte G.; Nørby, Peder Lisby; Clausen, Jes Thorn; Iversen, Lars

doi:10.1038/sj.jid.5700713

Cited by 54 publications

(74 citation statements)

References 40 publications

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“…These results extend observations on stimulation of IL-20 upon hypoxia (Chen and Chang, 2009) and UVB irradiation (Hunt, et al, 2006). Both IL-20 and IL-24 expression is dependent on p38 MAPK (Otkjaer, et al 2010;Otkjaer, et al, 2007), which is increased in KS cells (own unpublished results). This cytokine has been shown to specifically inhibit the activation of NF-kappaB induced by interleukin 1 family, member 6 (Blumberg, et al, 2007), but its contribution to KS phenotypes remains to be established.…”

Section: Inflammation and Dermal Fibrosis In Ks Skin In Vivosupporting

confidence: 77%

“…Thus far, little has been known about the functions of these cytokines in the skin. A recent study reported their induction after skin injury (Roupe, et al, 2010), and previous investigations suggested regulation of these interleukins through stress induced pathways (Chen and Chang, 2009;Hunt, et al, 2006;Otkjaer, et al, 2010;Otkjaer, et al, 2007). To corroborate this in KS, we used three different well-established methods -hypoxia, oxidative stress and UVB irradiation -to induce cell stress in normal and KS keratinocytes and showed that stress enhances expression and secretion of IL-20 and IL-24 by KS cells.…”

Section: Inflammation and Dermal Fibrosis In Ks Skin In Vivomentioning

confidence: 98%

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Induction of phenotype modifying cytokines by FERMT1 mutations

Heinemann

Зимина

et al. 2011

Hum. Mutat.

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Section: Inflammation and Dermal Fibrosis In Ks Skin In Vivosupporting

confidence: 77%

Section: Inflammation and Dermal Fibrosis In Ks Skin In Vivomentioning

confidence: 98%

Induction of phenotype modifying cytokines by FERMT1 mutations

Heinemann

Зимина

et al. 2011

Hum. Mutat.

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“…IL-20 is induced when IL-1␤ modulates p38 MAPK and the NF-B-dependent pathway (49). NF-B mediates ischemia-induced neuronal death via IB kinase (50).…”

Section: Discussionmentioning

confidence: 99%

IL-20 Is Regulated by Hypoxia-Inducible Factor and Up-Regulated after Experimental Ischemic Stroke

Chen

Chang

2009

The Journal of Immunology

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Stroke is the second leading cause of death and the leading cause of adult disability worldwide. Although different mechanisms are involved in the pathogenesis of stroke, increasing evidence shows that ischemic injury and inflammation account for its pathogenic progression (1, 2). Ischemic brain injury after stroke is a dynamic process that evolves over a period of hours to several days, particularly in the area surrounding the core of the infarct known as the penumbra (3). This process includes oxidative stress, cell death, and inflammation, as well as the activation of endogenous adaptive and regenerative mechanisms. The regulation of many of these processes occurs at the transcriptional level and involves the concerted activation of various transcription factors, including hypoxia-inducible factor 1␣ (HIF-1␣) 2 (4). Ischemic brain injury is a consequence of a severe reduction in the blood supply to the affected region. The deficits can often be permanent because adult neurons fail to regenerate. After they have been activated by injury, astrocytes and microglia release factors that recruit other astrocytes and microglia to the injury site. This process can lead to glial scar formation, which has the potential to block the growth and maturation of neural progenitors and to impede neovascularization, thus inhibiting recovery after injury (5).Cytokines are up-regulated in the brain in a variety of diseases, including stroke, and are expressed not only in the cells of the immune system, but are also produced by resident brain cells, including glia cells and neurons (6 -8). Chemokine expression precedes inflammatory cell infiltration following cerebral ischemia (9). IL-1␤ (10, 11), TNF-␣ (12, 13), , and MCP-1 (15) appear to exacerbate cerebral injury; however, TGF-␤ (16) and IL-10 (17) may be neuroprotective.The pleiotropic inflammatory cytokine IL-20, a member of IL-10 family which includes IL-10, IL-19, IL-20, IL-22, 19), is expressed in monocytes, epithelial cells, and endothelial cells and exerts its biological functions on multiple cell types by activating IL-20R1/IL-20R2 or IL-22R1/ . IL-20 is involved in various inflammatory diseases (21), such as psoriasis (18,22,23), rheumatoid arthritis (24), atherosclerosis (25,26), and renal failure (27). Recently, IL-20 has been reported to regulate angiogenesis (28,29). It is also an arteriogenic cytokine based on its actions in remodeling collateral networks and improving the functions of ischemic hind limbs (30).Our previous study showed that hypoxia induced IL-20 in endothelial cells (26). Little is known about the molecular mechanism of gene regulation of IL-20 in hypoxia and its clinical implications. In the present study, we found up-regulation of IL-20 under hypoxic conditions in vitro and in the ischemic brain in vivo. We identified IL-20 promoter regions and the functional response elements of the il20 gene in response to hypoxia. We also demonstrated a pathogenic role of IL-20 in ischemic brain injury in vivo using an animal model of transient middle cerebr...

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“…Cells were grown at 37˚C and 5% CO 2 in a humidified incubator. We have previously reported that this protocol routinely results in very pure keratinocyte cultures with .95% keratin 14-positive cells (21). Fresh medium was added every second day.…”

Section: Cellsmentioning

confidence: 99%

Inflammatory Cytokines Break Down Intrinsic Immunological Tolerance of Human Primary Keratinocytes to Cytosolic DNA

Chiliveru

Rahbek

Jensen

et al. 2014

The Journal of Immunology

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Keratinocytes are involved in protecting the body from infections and environmental challenges, but also in inflammatory conditions like psoriasis. DNA has emerged as a potent stimulator of innate immune responses, but there is largely no information of how keratinocytes respond to cytosolic DNA. In this study, we report that human keratinocytes are tolerant to cytoplasmic DNA. However, if treated with inflammatory cytokines, keratinocytes gained the capacity to respond to DNA through a mechanism antagonized by the antimicrobial peptide LL37, proposed to be involved in activation and regulation of skin inflammation. The DNA sensor IFN-inducible protein 16 (IFI16) colocalized with DNA and the signaling molecule stimulator of IFN genes (STING) in the cytoplasm only in cytokine-stimulated cells, correlating with recruitment of the essential kinase TANK-binding kinase 1. Moreover, IFI16 was essential for DNA-driven innate immune responses in keratinocytes. Finally, IFI16 was upregulated in psoriasis skin lesions and localized to the cytoplasm in a subpopulation of cells. Collectively, this work suggests that inflammatory environments in the skin can lead to breakdown of tolerance for DNA in keratinocytes, which could contribute to the development of inflammatory diseases.

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IL-20 Gene Expression Is Induced by IL-1β through Mitogen-Activated Protein Kinase and NF-κB-Dependent Mechanisms

Cited by 54 publications

References 40 publications

Induction of phenotype modifying cytokines by FERMT1 mutations

Induction of phenotype modifying cytokines by FERMT1 mutations

IL-20 Is Regulated by Hypoxia-Inducible Factor and Up-Regulated after Experimental Ischemic Stroke

Inflammatory Cytokines Break Down Intrinsic Immunological Tolerance of Human Primary Keratinocytes to Cytosolic DNA

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