|
KMID : 0032220210330020122
|
|
Annals of Dermatology
2021 Volume.33 No. 2 p.122 ~ p.130
|
|
|
I-Kappa-B-Zeta Regulates Interleukin-17A/Tumor Necrosis Factor-Alpha Mediated Synergistic Induction of Interleukin-19 and Interleukin-20 in Humane Keratinocytes
|
|
Bertelsen Trine
Iversen Lars
Johansen Claus
|
|
|
Abstract
|
|
|
Background: Interleukin (IL)-19 and IL-20 are important members of the IL-10 cytokine family, which are known to play a role in inflammatory processes. Both anti-IL-19 and -IL-20 targeting drugs have been suggested in the treatment of inflammatory diseases such as psoriasis and rheumatoid arthritis. Recently, we presented I-kappa-B-zeta (IκBζ) as a key player in psoriasis by identifying IκBζ as a regulator of IL-17/tumor necrosis factor (TNF)α-inducible psoriasis-associated genes and proteins. Some of these genes were synergistically regulated by IL-17/TNFα.
Objective: The purpose of this study was to explore the role of IκBζ in the regulation of IL-17A/TNFα-mediated induction of IL-19 and IL-20 expression in human keratinocytes.
Methods: In vitro experiments with cultured primary humane keratinocytes were conducted and investigated by quantitative polymerase chain reaction (qPCR), Western blotting, ELISA and EMSA. For statistics, a one- or two- way repeated-measures analysis of variance (RM ANOVA) or the Friedman test (a nonparametric equivalent to the RM ANOVA) were conducted.
Results: We demonstrated that IL-19 and IL-20 mRNA and protein expressions were synergistically induced by IL-17A and TNFα, whereas IL-17A and TNFα alone had only a minor effect on the IL-19 and IL-20 expression. Moreover, we demonstrated IκBζ to be a regulator of this synergistic induction of IL-19 and IL-20. Finally, the IL-17A/TNFα-induced synergistic induction of IL-19 and IL-20 expression was found to be mediated by a p38 MAPK-, NF-κB- and JNK1/2-dependent mechanism.
Conclusion: This study demonstrates that IκBζ plays a role in the IL-17A/TNFα-mediated synergistic induction of IL-19 and IL-20 in humane keratinocytes.
|
|
|
KEYWORD
|
|
|
I-kappa-B-zeta, Interleukin-17A, Interleukin-19, Interleukin-20, NFKBIZ
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
   
|