Inflammasomes are key innate immune system receptors that detect pathogenic endo-and exogenous stressors like microorganisms or ultraviolet radiation (UVR) which activate the highly proinflammatory cytokines interleukin-1β and interleukin-18. Inflammasomes are not only involved in inflammation, but also in carcinogenesis and tumor progression. Due to the dynamic increase in non-melanoma skin cancers (NMSC), it has become necessary to determine how UVR, which plays a key role in NMSC development, can regulate the structure and function of inflammasomes. In the present study, the regulatory mechanisms of NOD-Like Receptor Family Pyrin Domain Containing 1 and 3 inflammasome activation as well as an effective inflammasome-mediated immune response after UVR exposition are discussed. The differences and similarities between these molecular complexes that monitor cellular health, inflammation, and skin carcinogenesis are also highlighted. Despite numerous scientific data, more studies are still required to better understand the biology of inflammasomes in skin cancer development and to explore their therapeutic potential.
Basal cell carcinoma (BCC) is the most common skin malignancy type in the Caucasian population, with a continuously increasing incidence rate. The etiology of BCC remains unknown, but it appears to have a multifactorial origin resulting from intrinsic and extrinsic factors, including short-wavelength ultraviolet B radiation. The role of specific proteins in BCC that are known to be responsible for the regulation of cell division and are involved in skin aging, including transforming growth factor (TGF)-β, Smad2, matrix metalloproteinases (MMPs)-1, -3, -8 and -9, cathepsin-K and progerin, remains unknown. The aim of the present study was to assess the mRNA and protein expression profile of samples with diagnosed nodular BCC (nBCC) compared with that of healthy skin samples collected from matched areas. The study group included 22 patients (10 men and 12 women; mean age, 59 years; range, 44-82 years) with pathologically confirmed nBCC, and 22 healthy volunteers (10 men and 12 women; mean age, 59 years; range, 43-78 years) as a control group. The expression of the studied proteins was assessed in all samples by western blotting and reverse transcription-quantitative polymerase chain reaction analysis. Statistically significant increases in the expression of TGF-β, Smad2, cathepsin-K, progerin and MMP-1, -3, -8 and -9 were detected in skin biopsies with diagnosed nBCC compared with the control group, confirming the important role of these proteins in skin carcinogenesis.
Introduction 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. Aim 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. Material and methods 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. Results 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. Conclusions IL-18 and IL-20 as well as MMP-3 and COMP may be sensitive markers in the diagnosis of PsA.
IntroductionPustular palmoplantar psoriasis (PPP) is a rare type of psoriasis affecting mainly distal parts of the limbs. Despite numerous theories about etiology of PPP, the pathogenesis still remains unclear. Recent data indicate that interleukin (IL)-15, IL-17 and IL-22 enhance a proinflammatory response in certain skin inflammatory diseases such as psoriasis and atopic dermatitis. There is also evidence that anti-endomysial (anti-EMA) and anti-gliadin (AGA) antibodies are engaged in PPP development.AimTo assess IL-15, IL-17, IL-22 serum levels and evaluate the presence of anti-endomysial and anti-gliadin antibodies in patients with PPP.Material and methodsThe study group consisted of 20 females of the mean age of 51.8 suffering from PPP. Additionally 29 healthy individuals, age and sex matched, served as controls. ELISA was performed to evaluate serum IL-15, IL-17, IL-22 concentrations while an indirect immunofluorescence test (IIF) was used to determine anti-EMA and AGA presence.ResultsThe mean value of IL-15 and IL-22 serum concentrations was significantly higher in the study group than in the control group (IL-15: 6.48 vs. 4.88 pg/ml; IL-22: 81.47 vs. 4.90 pg/ml, respectively; p < 0.05 for all comparisons). The IL-17 serum level in the study group was higher when compared to the control group (2.0 vs. 0.75 pg/ml), however the results were not statistically significant (p = 0.26). There were no anti-EMA and AGA antibodies detected, both in the control and study group.ConclusionsThe results obtained may suggest involvement of IL-15 and IL-22 in the pathogenesis of PPP.
Introduction: 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. Material and methods: 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 (WOM-AC) and Lequesne Index. Results: 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). Conclusions: 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.
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