Interleukin-19 (IL-19) and Interleukin-20 (IL-20) are inflammatory cytokines belonging to the IL-10 family with immunoregulatory properties. Emerging evidence highlights the importance of association of these cytokines with both immunological and inflammatory disorders, including chronic inflammation, cardiac dysfunction, and cancer. IL-19 and IL-20 bind to the heterodimeric receptor complex and induce multiple downstream signaling cascades by activating the signal transducer and activator of transcription 3 (STAT3), Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT1), and NFKB inhibitor alpha (NFKBIA), leading to proinflammatory and anti-inflammatory reactions in cancer, inflammation, tumor microenvironment, and infectious diseases. Considering the significant role of these cytokines, we integrated its cellular signaling network by combining multiomics molecular events associated with 56 molecules of induced by IL-19 and 156 molecules of by IL-20. The reactions of these signaling events are classified into enzyme catalysis/post-translational modifications, activation/inhibition events, molecular associations, gene regulations at the mRNA and protein level, and the protein translocation events. We believe that this signaling pathway map would serve as a knowledge base, that aid researchers and clinicians to understand and explore the intricate mechanisms and identify novel signaling components and therapeutic targets for diseases associated with dysregulated IL-19 and IL-20 signaling.

Interleukin-20 (IL-20), as an essential member of IL-10 family, plays vital roles in mammalian immunological response such as antimicrobial, inflammation, hematopoiesis, and immune diseases. In teleost, the study about immune antimicrobial function of IL-20 is largely scarce. In this article, we revealed the expression profiles and the immunological functions of the IL-20 (CsIL-20) in tongue sole Cynoglossus semilaevis. CsIL-20 is composed of 183 amino acid residues, with seven cysteine residues and a typical IL-10 domain which comprises six α-helices and two β-sheets, and shares 34.4-71.2 % identities with other teleost IL-20. CsIL-20 was constitutively expressed in a variety of tissues and regulated by bacterial invasion, and the recombinant CsIL-20 (rCsIL-20) could bind to different bacteria. In vitro rCsIL-20 could interact with the membrane of peripheral blood leukocytes (PBLs), leading to the attenuation of reactive oxygen species (ROS) production and acid phosphatase activity in PBLs. In line with In vitro results, In vivo rCsIL-20 could obviously suppressed the host immune against bacterial infection. Furthermore, knockdown of CsIL-20 in vivo could markedly enhance the host antibacterial immunity. Collectively, these observations offer new insights into the negative effect of CsIL-20 on antibacterial immunity.

Osteoimmunology mediators are critical to balance osteoblastogenesis and osteoclastogenesis to maintain bone homeostasis. A lot of the osteoimmunology mediators are regulated by interleukin-20 (IL-20). However, little is known about the role of IL-20 in bone remodeling. Here, we showed that IL-20 expression was correlated with osteoclast (OC) activity in remodeled alveolar bone during orthodontic tooth movement (OTM). Ovariectomize (OVX) in rats promoted OC activity and enhanced IL-20 expression, while blocking OC inhibited IL-20 expression in osteoclasts. In vitro, IL-20 treatment promoted survival, inhibited apoptosis of the preosteoclast at the early stages of osteoclast differentiation, and boosted the formation of osteoclasts and their bone resorption function at the late stages. More importantly, anti-IL-20 antibody treatment blocked IL-20-induced osteoclastogenesis and the subsequent bone resorption function. Mechanistically, we showed that IL-20 synergistically acts with RANKL to activate the NF-κB signaling pathway to promote the expression of c-Fos and NFATc1 to promote osteoclastogenesis. Moreover, we found that local injection of IL-20 or anti-IL-20 antibody enhanced osteoclast activity and accelerated OTM in rats, while blocking IL-20 reversed this phenomenon. This study revealed a previously unknown role of IL-20 in regulating alveolar bone remodeling and implies the application of IL-20 to accelerated OTM.

As an inflammatory cytokine of the interleukin-20 (IL-20) subfamily, IL-20 has various functions in immune defenses, inflammatory diseases, tissue regeneration, cancer, and metabolism. Although the characteristics and functions of mammalian IL-20 have been clarified, those of fish IL-20 remain unclear. In this study, the IL-20 gene from the snakehead Channa argus (shIL-20) was cloned and functionally characterized. Similar to the IL-20 homologues of other species, the shIL-20 has a five exon/four intron structure in the coding region. The open reading frame of shIL-20 consists of 528 base pairs and encodes 175 amino acids (aa), including a signal peptide (aa 1-24) and a mature peptide (aa 25-175). The mature shIL-20 protein has six conserved cysteine residues, which occur in the IL-20 proteins of all species analyzed, and an additional cysteine residue (Cys-82) found only in the IL-20 proteins of several teleosts. The modeled tertiary structure of shIL-20 is similar with that of Homo sapiens IL-20. The shIL-20 was expressed constitutively in all the tissues analyzed, and its transcription was induced in the spleen and head kidney by Aeromonas schubertii and Nocardia seriolae in vivo and in head kidney leukocytes (HKLs) by lipoteichoic acid, lipopolysaccharide, and polyinosinic-polycytidylic acid in vitro. The recombinant shIL-20 protein induced the transcription of tumor necrosis factor α1 (TNF-α1), TNF-α2, IL-1β, and endogenous shIL-20, and promoted the proliferation of HKLs. In conclusion, these findings demonstrate that shIL-20 participates in the immune response to bacterial invasion and promotes leukocyte proliferation, offering new insights into the functions of fish IL-20 during pathogen invasion.

UNASSIGNED: Osteoarthritis (OA) is the most common degenerative joint disease, and its aetiology is not entirely known. The aim of the study was to evaluate the involvement of interleukin-18 (IL-18) and interleukin-20 (IL-20) in the pathogenesis of knee OA and their correlations with other markers of inflammation and destruction of joint cartilage, as well as clinical and radiological changes.
UNASSIGNED: The study included 25 patients with knee OA and a control group. The concentration of IL-18, IL-20, IL-6, MMP-1, MMP-3, COMP, PG-AG, and YKL-40 in serum and synovial fluid (SF) were determined. We also evaluated radiological lesions of the knee joint according to the Kellgren-Lawrence (K-L) scale, and clinical severity of the disease according to Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne Index.
UNASSIGNED: The concentrations of IL-18 and IL-20 were statistically significantly higher in serum of patients with OA than in the control group (106.00 ±189.76 pg/ml vs. 16.73 ±16.99 pg/ml, p < 0.001, 17.69 ±13.45 pg/ml vs. 9.76 ±9.00 pg/ml, p < 0.014). Serum concentration of IL-18 positively correlated with MMP-3 (R = 0.58; p = 0.006) and YKL-40 (R = 0.48; p = 0.002). The degree of radiological advancement of OA (K-L scale) correlated positively with clinical evaluation (WOMAC, R = 0.74, p ≤ 0.001; Lequesne Index, R = 0.57, p = 0.003).
UNASSIGNED: The analysis of ROC curves showed that IL-20 as well as COMP, MMP-3, and YKL-40 may be diagnostic markers of knee OA. The observations indicate that IL-18 potentially mediates mainly in intra-articular processes and IL-20 could be primarily responsible for the systemic inflammatory reaction.

The eye is regarded as an immune privileged site. Since the presence of a vasculature would impair vision, the vasculature of the eye is located outside of the central light path. As a result, many regions of the eye evolved mechanisms to deliver immune cells to sites of dysgenesis, injury, or in response to the many age-related pathologies. While the purpose of these immune responses is reparative or protective, cytokines released by immune cells compromise visual acuity by inducing inflammation and fibrosis. The response to traumatic or pathological injury is distinct in different regions of the eye. Age-related diseases impact both the anterior and posterior segment and lead to reduced quality of life and blindness. Here we focus attention on the role that inflammation and fibrosis play in the progression of age-related pathologies of the cornea and the lens as well as in glaucoma, the formation of epiretinal membranes, and in proliferative vitreoretinopathy.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

OBJECTIVE: To investigate the effects of interleukin-20 (IL-20) on the osteogenic differentiation of MC3T3-E1 cells.
METHODS: The pre-osteoblast line MC3T3-E1 was treated with different concentrations of IL-20 (0, 2, 20 and 100 ng/mL), and the cell viability was detected by the CCK8 assay. To assess the influence of IL-20 on osteogenic differentiation, alkaline phosphatase (ALP) activity and Alizarin red staining were performed at predetermined times. The expression levels of Runt-related transcription factor 2 (RUNX2), Osterix (Osx), glycogen synthase kinase-3β (GSK-3β) and β-catenin were detected by qRT-PCR and Western blotting analyses. 5 nmol/L lithium chloride (LiCl) was used as GSK-3β inhibitor.
RESULTS: IL-20 promoted cell proliferation but decreased ALP activity and mineralization. Moreover, IL-20 downregulated the expression of RUNX2, Osx and β-catenin but upregulated the level of GSK-3β.
CONCLUSIONS: The results suggest that IL-20 could inhibit the osteogenic differentiation of MC3T3-E1 cells via the GSK3β/β-catenin signalling pathway.

UNASSIGNED: Psoriatic arthritis (PsA) is a chronic, seronegative spondyloarthropathy characterised by joint inflammation and psoriatic skin changes. Recent data indicate that interleukin-18 (IL-18) and interleukin-20 (IL-20) may be involved in the aetiopathogenesis of PsA.
UNASSIGNED: To evaluate the potential role of IL-18, IL-20, and matrix metalloproteinases (MMP-1, MMP-3) in the pathogenesis of PsA and their correlations with other markers of inflammation and destruction of joint cartilage, as well as clinical changes.
UNASSIGNED: The study included 24 patients with PsA and 26 healthy volunteers as a control group. The concentration of IL-18 and IL-20, c-reactive protein (CRP), metalloproteinase-1 and -3 (MMP-1, MMP-3), cartilage oligomeric matrix protein (COMP), aggrecan (PG-AG), and human cartilage glycoprotein (YKL-40) in serum was determined. Clinical severity of the disease according to the BSA, PASI, and DLQI as well as tender and swollen joint count (TJC, SJC) were also evaluated.
UNASSIGNED: The concentration of IL-18 was statistically significantly higher in the serum of patients with PsA than in the control group (62.87 pg/ml vs. 16.73 pg/ml, p < 0.0049). Serum IL-20 levels in PsA patients were also higher than in the control group, but without statistical significance (p = 0.2939). The ROC curves showed: AUC = 0.81 for IL-18, AUC = 0.75 for IL-20, AUC = 0.96 for COMP, and AUC = 0.89 for MMP-3.
UNASSIGNED: IL-18 and IL-20 as well as MMP-3 and COMP may be sensitive markers in the diagnosis of PsA.

BACKGROUND: Interleukin-20 (IL-20) is closely related to cardiovascular diseases such as atherosclerosis. The relevance of IL-20 expression in human chronic heart failure (CHF) remains unknown. Thus, we investigated the level of circulating IL-20 in CHF patients and observed its correlation with CHF outcomes.
METHODS: A cohort study was performed with CHF patients. Blood samples of 180 CHF patients and 167 control subjects were collected, and the plasma IL-20 level of each patient was determined. In addition, the endpoints of cardiovascular events among the CHF patients were evaluated prospectively. The maximum follow-up time of these CHF patients was 24 months, and the median follow-up time was 21 months.
RESULTS: IL-20 levels were high in CHF patients and gradually increased in the New York Heart Association (NYHA) functional class II, the NYHA III and the NYHA IV groups. According to the low, middle and high tertiles of IL-20 levels, the CHF patients were respectively divided into groups 1, groups 2, and groups 3. Multivariate Cox hazard analysis showed that the group 3 exhibited significantly higher cardiac event morbidity than the other two groups after adjustment for confounding factors. The CHF patients were also divided into two groups according to plasma IL-20 levels, and higher rates of cardiovascular events were observed in the group with higher IL-20 levels.
CONCLUSIONS: Circulating IL-20 levels are significantly elevated in CHF patients, and higher IL-20 levels suggest poorer outcomes in CHF patients.