Psoriasis is a chronic, inflammatory skin disease involving both environmental and genetic factors. According to genome-wide association studies (GWAS), the TNIP1 gene, which encodes the TNF-α–induced protein 3-interacting protein 1 (TNIP1), is strongly linked to the susceptibility of psoriasis. TNIP1 is a widely expressed ubiquitin sensor that binds to the ubiquitin-editing protein A20 and restricts TNF- and TLR-induced signals. In our study, TNIP1 expression decreased in specimens of epidermis affected by psoriasis. Based on previous studies suggesting a role for TNIP1 in modulating cancer cell growth, we investigated its role in keratinocyte proliferation, which is clearly abnormal in psoriasis. To mimic the downregulation or upregulation of TNIP1 in HaCaT cells and primary human keratinocytes (PHKs), we used a TNIP1 specific small interfering hairpin RNA (TNIP1 shRNA) lentiviral vector or a recombinant TNIP1 (rTNIP1) lentiviral vector, respectively. Blocking TNIP1 expression increased keratinocyte proliferation, while overexpression of TNIP1 decreased keratinocyte proliferation. Furthermore, we showed that TNIP1 signaling might involve extracellular signal-regulated kinase1/2 (Erk1/2) and CCAAT/enhancer-binding protein β (C/EBPβ) activity. Intradermal injection of TNIP1 shRNA in BALB/c mice led to exaggerated psoriatic conditions in imiquimod (IMQ)-induced psoriasis-like dermatitis. These findings indicate that TNIP1 has a protective role in psoriasis and therefore could be a promising therapeutic target.

To evaluate the therapeutic efficacy and safety of anti-IL-17 agents in the treatment of psoriasis, we performed a systemic review and meta-analysis of the relevant published clinical trials, collectively referred to as secukinumab, ixekizumab and brodalumab. 2668 patients in eight eligible trials with psoriasis were selected for the present meta-analysis. The estimated pooled PASI75, PSAI90, physician's global assessment (PGA; clear) showed significant improvements for psoriasis patients who received biotherapy compared with placebo. The results of headache, upper respiratory tract infection and infections demonstrated that there was no significant difference between the biotherapy and placebo groups. But the results of nasopharyngitis demonstrated that there was a significant difference for biotherapy group. The results showed that anti-IL-17 agents were effective and safe for psoriasis patients.

No abstract

The aberrantly activated monocytes and nuclear factor-kappaB (NF-κB) pathway contribute to the pathogenesis of systemic lupus erythematosus (SLE), and the aberrantly activated NF-κB is associated with defects in the anti-inflammatory A20 in SLE. However, whether SLE monocytes express A20 and whether the A20 expression under sustained proinflammatory stimulation is altered to contribute to the uncontrolled NF-κB inflammatory response are unclear. In this study, we found that the freshly isolated monocytes from SLE patients and healthy controls did not differ in expression levels of IL-1β, IκBα and A20. After TNF-α stimulation for 48 h, the monocytes from both groups expressed higher levels of IL-1β and IκBα than the monocytes without TNF-α treatment. Although the increased levels of NF-κB were observed in the nucleus of both the SLE and control monocytes after 24 h of TNF-α stimulation, the enhancement in SLE monocytes was significantly more robust than in the control monocytes. In addition, while the p-IκBα level in healthy monocytes was increased, the p-IκBα level in SLE monocytes was slightly decreased after TNF-α stimulation. Interestingly, after TNF-α treatment, the A20 expression in SLE monocytes was not markedly altered compared with the untreated SLE monocytes; moreover, the SLE monocytes expressed significantly lower A20 than healthy monocytes with TNF-α treatment at each time point. Results in this study demonstrate that TNF-α activates a significant NF-κB inflammatory response in SLE monocytes, which is at least partially mediated by the aberrantly low expression of A20 upon TNF-α stimulation, contributing to the prolonged inflammatory response in SLE.

No abstract

C/EBP β/TNFAIP3/TNIP1 is associated with SLE activity. The upregulated expression of C/EBP β LAP could be caused by reduced TNFAIP3/TNIP1 expression.

BackgroundAtopic dermatitis (AD) is a common inflammatory skin disease, with the incidence peaks in infancy. A meta-analysis was performed to assess the levels of T helper type 22 (Th22) cells, T helper type 17 (Th17) cells, interleukin (IL)-17, and Tregs in peripheral blood of patients with AD.MethodsA comprehensive literature search was performed in PubMed, Embase, China National Knowledge Internet, and Wan-fang Data from the day of inception of this study to July 2021. Two authors independently extracted the data, which were pooled and calculated using Stata software version 15.ResultsA total of eight studies met the inclusion criteria. Compared with control group, patients with AD had an increased proportion of Th22 cells [weighted mean difference (WMD) = 2.07, 95% CI (1.33, 2.81), p < 0.001], Th17 cells [WMD = 1.04, 95% CI [0.66, 1.43], p < 0.001], IL-17 [WMD = 17.56, 95% CI (11.1, 24.03), p < 0.001], and a decreased proportion of Tregs [WMD = −2.49, 95% CI (−2.93, −2.05), p < 0.001] in peripheral blood. The subgroup analysis showed that patients with higher disease severity had higher levels of Th22 [mild: WMD = 1.33, 95% CI (1.24, 1.41), p < 0.001; moderate: WMD = 1.41, 95% CI (1.36, 1.54), p < 0.001; severe: WMD = 3.46, 95% CI (3.34, 2.81), p < 0.001] and lower levels of Tregs [mild: WMD = −1.43, 95% CI (−1.75, −1.11), p < 0.001; moderate: WMD = −2.16, 95% CI (−2.46, −1.86), p < 0.001; severe: WMD = −2.96, 95% CI (−3.25, −2.67), p < 0.001] in peripheral blood compared to healthy controls.ConclusionThe random effect model of the meta-analysis showed patients with AD had an increased proportion of Th22 cells, Th17 cells, and IL-17, whereas a decreased proportion of Tregs was found in peripheral blood. The results demonstrated that Th22 cells, Th17 cells, IL-17, and Tregs may be involved in the pathogenic mechanisms of AD.

Abstract. CCAAT/enhancer-binding protein β (C/EBP β) has important roles in numerous signaling pathways. The expression of the majority of regulators and target gene products of C/EBP β, including tumor necrosis factor α-induced protein 3 (TNFAIP3) and TNFAIP3-interacting protein 1 (TNIP1), are upregulated in patients with systemic lupus erythematosus (SLE). The aim of the present study was to investigate whether C/EBP β expression is associated with SLE pathogenesis and correlates with TNIP1 and TNFAIP3 expression. Quantitative reverse transcription-polymerase chain reaction analysis was used to assess the expression of C/EBP β, TNIP1, and TNFAIP3 mRNA in peripheral blood mononuclear cells (PBMC) from 20 patients with SLE and 20 healthy controls. Spearman's rank test was used to determine the correlation between C/EBP β expression and SLE disease activity, and that between C/EBP β expression and TNIP1/TNFAIP3 expression in PBMCs from patients with SLE. C/EBP β mRNA expression was markedly increased in patients with SLE compared with healthy controls. The expression of C/EBP β was positively correlated with the SLE disease activity index and negatively correlated with the serum level of complement components C3 and C4. In addition, C/EBP β mRNA expression was increased in PBMCs from SLE patients that were positive for antinuclear, anti-Smith and anti-nRNP antibodies, compared with the antibody negative SLE patients. Furthermore, the mRNA expression levels of C/EBP β in patients with SLE was positively correlated with TNIP1 and TNFAIP3 expression.The results of the current study suggest that the increased expression of C/EBP β in PBMCs and the interaction between C/EBP β and TNIP1/TNFAIP3 may be involved in the pathogenesis of SLE. IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and is characterized by chronic inflammation with autoantibody production. The pathogenesis of SLE is complex and involves numerous immune cells and cytokines. B cells are known to have an essential role in autoantibody production in autoimmune disease (1). In addition, T cells have been recognized as a crucial component in the pathogenicity of SLE through their communication with B cells, which helps drive autoantibody production (2). In recent years, the importance of innate immunity in SLE pathogenesis has become increasingly evident, particularly regarding the role of Toll-like receptor (TLR) signaling pathways (3,4). Furthermore, the abnormal expression of certain cytokines and their receptors leads to immune hyperactivity in SLE; thus, cytokines such as interferon (IFN)-α, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) are considered to be therapeutic targets for SLE (5).Previous studies have determined that several cytokine genes are regulated by CCAAT/enhancer-binding protein β [C/EBP β, also known as nuclear factor for IL 6, cysteine rich protein 2, IL-6DBP, liver-enriched activating protein (LAP), NF-M, α1 acid glycoprotein/enhancer-binding protein, or ApC/EBP), which ...