A Heterodimeric Cytokine, Consisting of IL-17A and IL-17F, Promotes Migration and Capillary-Like Tube Formation of Human Vascular Endothelial Cells

Numasaki, Muneo; Tsukamoto, Hiroki; Tomioka, Y.; Nishioka, Yasuhiko; Ohrui, Takashi

doi:10.1620/tjem.240.47

Cited by 15 publications

(10 citation statements)

References 46 publications

(48 reference statements)

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“…In agreement with other studies, we present the IL‐17A/F heterodimer as an IL‐17 cytokine that mimics the effect of both IL‐17A/A and IL‐17F/F and we extent the current understanding of the regulation of psoriasis in relation to IκBζ. In this study, we further extend the characterization of the IL‐17A/F heterodimer by investigating the effect of different concentrations on the NFKBIZ mRNA expression.…”

Section: Resultssupporting

confidence: 92%

The human IL‐17A/F heterodimer regulates psoriasis‐associated genes through IκBζ

Bertelsen

Iversen

Johansen

2018

Experimental Dermatology

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Antagonists of IL-17A and its receptor have proven to be highly effective in the treatment of psoriasis. However, many of the underlying molecular mechanisms involved in the pathogenesis of psoriasis are still to be determined. IκBζ (encoded by the NFKBIZ gene) plays a key role in the development of psoriasis by mediating IL-17A- and IL-17F-driven effects. Both IL-17A and IL-17F expression are increased in lesional psoriatic skin. IL-17A/A and IL-17F/F homodimers as well as the IL-17A/F heterodimer signal through the same receptors. The aim of this study was to characterize the role of the IL-17A/F heterodimer in the regulation of NFKBIZ expression and in the regulation of selected psoriasis-associated genes. We demonstrated that IL-17A/F stimulation of human keratinocytes significantly induced NFKBIZ expression. Moreover, silencing IκBζ by siRNA revealed that IκBζ is a key regulator of IL-17A/F-inducible psoriasis-associated genes, including CCL20, DEFB4, IL-8, CHI3L1 and S100A7. In addition, IL-17A/F-induced NFKBIZ expression was mediated by a mechanism involving the p38 MAPK and NF-κB signalling pathways. In conclusion, we present IκBζ as a novel key regulator of IL-17A/F-driven effects in psoriasis. Thus, antagonists to IL-17A/F or IκBζ may present a targeted approach for treating psoriasis.

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Section: Resultssupporting

confidence: 92%

The human IL‐17A/F heterodimer regulates psoriasis‐associated genes through IκBζ

Bertelsen

Iversen

Johansen

2018

Experimental Dermatology

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“…Endothelial cells are the main cellular component of the lining of blood vessels. Among the members of IL-17 family, IL-17A, IL-17A/F heterodimer and IL-17E/IL-25 are angiogenesis stimulants, while IL-17B and IL-17F are angiogenesis inhibitors ( 58 ). Vascular endothelial cells are one of the cell types that produce CXC chemokines.…”

Section: Effects Of Il-17a On Other Cellsmentioning

confidence: 99%

Role of Interleukin-17A in the Pathomechanisms of Periodontitis and Related Systemic Chronic Inflammatory Diseases

Feng

Chen

et al. 2022

Front. Immunol.

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Periodontitis is a chronic inflammatory and destructive disease caused by periodontal microbial infection and mediated by host immune response. As the main cause of loosening and loss of teeth in adults, it is considered to be one of the most common and serious oral diseases in the world. The co-existence of periodontitis and systemic chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, diabetes and so on is very common. It has been found that interleukin-17A (IL-17A) secreted by various innate and adaptive immune cells can activate a series of inflammatory cascade reactions, which mediates the occurrence and development of periodontitis and related systemic chronic inflammatory diseases. In this work, we review the role of IL-17A in the pathomechanisms of periodontitis and related systemic chronic inflammatory diseases, and briefly discuss the therapeutic potential of cytokine targeted agents that modulate the IL-17A signaling. A deep understanding of the possible molecular mechanisms in the relationship between periodontitis and systemic diseases will help dentists and physicians update their clinical diagnosis and treatment ideas.

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“…In this respect, IL-17 has been shown to directly induce VEGF in several malignant cell lines, including gastric ( Meng et al, 2012 ), breast ( Amara et al, 2016 ), and lung cancer ( Pan et al, 2015b ; Huang et al, 2016 ), as well as in tumor-associated neutrophils ( Benevides et al, 2015 ). IL-17 can also stimulate VEGF release by normal fibroblasts from the lung, skin, and cornea ( Numasaki et al, 2004 , 2016 ; Suryawanshi et al, 2012 ), by synoviocytes ( Honorati et al, 2006 ; Ryu et al, 2006 ), and chondrocyte-like cells from the nucleus pulposus ( Hu et al, 2016 ). Such an effect, however, does not seem to be a general phenomenon, as VEGF secretion was not detected in IL-17-stimulated dermal microvascular endothelial cells ( Takahashi et al, 2005 ) and in a number of cancer cell lines ( Wu et al, 2016 ).…”

Section: Il-17 In Angiogenesismentioning

confidence: 99%

IL-17 in Peritoneal Dialysis-Associated Inflammation and Angiogenesis: Conclusions and Perspectives

et al. 2018

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Long-term peritoneal dialysis (PD) is associated with peritoneal membrane remodeling. This includes changes in peritoneal vasculature, which may ultimately lead to inadequate solute and water removal and treatment failure. The potential cause of such alterations is chronic inflammation induced by repeated episodes of infectious peritonitis and/or exposure to bioincompatible PD fluids. While these factors may jeopardize the peritoneal membrane integrity, it is not clear why adverse peritoneal remodeling develops only in some PD patients. Increasing evidence points to the differences that occur between patients in response to the same invading microorganism and/or the differences in the course of inflammatory reaction triggered by different species. Such differences may be related to the involvement of different inflammatory mediators. Here, we discuss the potential role of IL-17 in these processes with emphasis on its impact on peritoneal mesothelial cells and peritoneal vascularity.

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A Heterodimeric Cytokine, Consisting of IL-17A and IL-17F, Promotes Migration and Capillary-Like Tube Formation of Human Vascular Endothelial Cells

Cited by 15 publications

References 46 publications

The human IL‐17A/F heterodimer regulates psoriasis‐associated genes through IκBζ

The human IL‐17A/F heterodimer regulates psoriasis‐associated genes through IκBζ

Role of Interleukin-17A in the Pathomechanisms of Periodontitis and Related Systemic Chronic Inflammatory Diseases

IL-17 in Peritoneal Dialysis-Associated Inflammation and Angiogenesis: Conclusions and Perspectives

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