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 psoriasisassociated 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.

No abstract available.
Digoxin* ; Ear* ; Inflammation* ; Skin*

Bacteria survive in nature by forming biofilms on surfaces and probably most, if not all, bacteria (and fungi) are capable of forming biofilms. A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and extracellular DNA. Bacterial biofilms are resistant to antibiotics, disinfectant chemicals and to phagocytosis and other components of the innate and adaptive inflammatory defense system of the body. It is known, for example, that persistence of staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infections in cystic fibrosis patients are caused by biofilm growing mucoid strains. Gradients of nutrients and oxygen exist from the top to the bottom of biofilms and the bacterial cells located in nutrient poor areas have decreased metabolic activity and increased doubling times. These more or less dormant cells are therefore responsible for some of the tolerance to antibiotics. Biofilm growth is associated with an increased level of mutations. Bacteria in biofilms communicate by means of molecules, which activates certain genes responsible for production of virulence factors and, to some extent, biofilm structure. This phenomenon is called quorum sensing and depends upon the concentration of the quorum sensing molecules in a certain niche, which depends on the number of the bacteria. Biofilms can be prevented by antibiotic prophylaxis or early aggressive antibiotic therapy and they can be treated by chronic suppressive antibiotic therapy. Promising strategies may include the use of compounds which can dissolve the biofilm matrix and quorum sensing inhibitors, which increases biofilm susceptibility to antibiotics and phagocytosis.
Animals ; Antibiotic Prophylaxis ; Biofilms ; drug effects ; growth & development ; Chronic Disease ; Cystic Fibrosis ; microbiology ; Drug Resistance, Microbial ; physiology ; Foreign Bodies ; microbiology ; Humans ; Microbial Consortia ; drug effects ; genetics ; immunology ; Phagocytosis ; Pseudomonas Infections ; microbiology ; Pseudomonas aeruginosa ; drug effects ; genetics ; physiology ; Quorum Sensing ; drug effects ; genetics