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Background A role for the innate immune system in driving the autoimmune T cell cascade in psoriasis has been proposed. Toll-like receptors-(TLR)-2 and -4 play a role in inflammation, atherosclerosis, and their specific role in psoriasis remains unclear. Objective To evaluate TLR2 and TLR4 gene expression levels in peripheral blood mononuclear cells from psoriatic patients. Methods Changes in TLR2/4 gene expressions were evaluated using quantitative real-time reverse transcription polymerase chain reaction in peripheral blood mononuclear cells, from twenty-one patients with severe psoriasis, and analysed whether there was any correlation with cytokine plasma levels (T-helper 0-, T-helper 1-, T-helper 2- or regulatory T cells-type), or Calprotectin and with S100A8 and S100A9 gene expression levels. Eleven non-psoriatic healthy controls were analysed. Results A clear increase in TLR4 gene expression was observed (3.84 ± 0.93, n = 21) together with a moderate increase in TLR2 expression (1.522 ± 0.31, n = 21). Both TLR4 and TLR2 gene expressions were significantly augmented in psoriatic patients compared with controls (all P < 0.001). Correlations between TLR2 and S100A9 gene expressions (r = 0.5145, P = 0.0170, n = 21); and between TLR2 expression and plasma interleukin-2 (r = 0.5667, P = 0.0074); interleukin-4 (r = 0.4766, P = 0.0289), interleukin-10 (r = 0.4355, P = 0.0484) and interleukin-13 (r = 0.4603, P = 0.0358), were found. When patients with atheroma plaque were considered (n = 7), both TLR4 (3.47 ± 0.99, P = 0.0156) and TLR2 (1.63 ± 0.31, P = 0.0156) expressions were significantly increased vs. controls and correlated with plasma TNF-α (r = 0.8929, P = 0.0123, in both cases). Conclusion Differential TLR4/2 gene expressions on psoriatic peripheral blood mononuclear cells and correlations with regulatory and/or proinflammatory cytokines and/or damage-associated molecular pattern molecule S100A9 emphasize innate immune response role in psoriasis.
Department of Cellular Biology and Immunology, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, P.T. Ciencias de la Salud, Armilla, Granada, Spain Department of Dermatology Department of Radiology, San Cecilio Un
This article was published in the following journal.
Name: Journal of the European Academy of Dermatology and Venereology : JEADV
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A pattern recognition receptor that forms heterodimers with TOLL-LIKE RECEPTOR 2.
A pattern recognition receptor that forms heterodimers with other TOLL-LIKE RECEPTORS. It interacts with multiple ligands including PEPTIDOGLYCAN, bacterial LIPOPROTEINS, lipoarabinomannan, and a variety of PORINS.
A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.
The expression of a gene in an abnormal place, or at an abnormal time in an organism. Ectopic Gene Expression is often induced artificially by genetic techniques.
A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.
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