Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown aetiology. The results of experimental studies point to the involvement of innate immunity receptors—toll-like receptors (TLR)—in the pathogenesis of the disease. The aim of the study was to assess the expression of TLR3, 7, and 9 in the population of peripheral blood mononuclear cells (PBMC) and in B lymphocytes (CD19+), T lymphocytes (CD4+ and CD8+) using flow cytometry. The study group included 35 patients with SLE and 15 healthy controls. The patient group presented a significantly higher percentage of TLR3- and TLR9-positive cells among all PBMCs and their subpopulations (CD3+, CD4+, CD8+, and CD19+ lymphocytes) as well as TLR7 in CD19+ B-lymphocytes, compared to the control group. There was no correlation between the expression of all studied TLRs and the disease activity according to the SLAM scale, and the degree of organ damage according to the SLICC/ACR Damage Index. However, a correlation was observed between the percentage of various TLR-positive cells and some clinical (joint lesions) and laboratory (lymphopenia, hypogammaglobulinemia, anaemia, and higher ESR) features and menopause in women. The results of the study suggest that TLR3, 7, and 9 play a role in the pathogenesis of SLE and have an impact on organ involvement in SLE.
Toll-like receptors (TLR), especially TLR3, 7 and 9, play an important role in the pathogenesis of systemic lupus erythematosus (SLE). In our study blood was collected from 16 patients with SLE and from 8 healthy volunteers. Concentrations of IL-6, IL-10 and sIL-2R were measured by ELISA in mononuclear cell culture supernatant after 24 hours of stimulation by agonists and antagonists of TLR3 and 9 (for TLR3-poli I/C, resveratrol and for TLR9-ODN2006, IRS 945). Stimulation of TLR9 by ODN2006 led to an increase of IL-6 concentration in cell culture supernatants from the cells of healthy volunteers compared with unstimulated cells from controls. Inhibition of TLR3 activation by resveratrol caused a significantly lower concentration of IL-10 in cell culture supernatants derived from both patients and healthy donors. Moreover, resveratrol significantly decreased the level of IL-10 and sIL-2R in culture supernatants of cells derived from patients with active disease compared to the inactive stage. A positive correlation was also found between IL-6 concentration following ODN2006 administration and disease activity. In conclusions, our results indicate that TLRs play a role in the modulation of the inflammatory response in SLE patients. This suppressive action on IL-10 synthesis demonstrated by resveratrol suggests that it may be useful in SLE therapy.
The article is a review of information concerning etiopathogenesis of systemic lupus erythematosus (SLE). Due to the risk of serious complications, including death, the clarification of etiology could result in substantial improvement or even complete cure of the disease. Progress in scientific research of observed disorder mechanisms together with implementation of appropriate therapies contributed to a higher detection rate, improved course and decreased mortality in SLE. However, there are still many doubts, which legitimate the need of further research. A significant role in development of the disease and further exacerbations is played by environmental factors. Therefore, decreased exposure to UV light, female sex hormone and microbial antigens is associated with improved course and decreased frequency of exacerbations. Less is known about the genetic basis of SLE, which results from a multigene disease background and complex hereditary mechanisms. It is estimated that the disease may be conditioned by around 100 genes, that only in part are functionally determined. Only part of them is already functionally characterized. The role played by most of them is still unknown. Research currently being conducted is aimed at detecting genetic polymorphism in large and genetically diverse populations. It will allow evaluation of the role of a particular gene in protein biosynthesis, which is responsible for development of regulatory process disturbances, commonly observed in the course of SLE. The article presents current directions of research and the latest advances in epidemiology as well as environmental and genetic risk factors of SLE.
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