IL-26 Is Overexpressed in Rheumatoid Arthritis and Induces Proinflammatory Cytokine Production and Th17 Cell Generation

Interleukin-26 (IL-26), a member of the IL-10 cytokine family, induces the production of proinflammatory cytokines by epithelial cells. IL-26 has been also reported overexpressed in Crohn\u27s disease, suggesting that it may be involved in the physiopathology of chronic inflammatory disorders. Here, we have analyzed the expression and role of IL-26 in rheumatoid arthritis (RA), a chronic inflammatory disorder characterized by joint synovial inflammation. We report that the concentrations of IL-26 are higher in the serums of RA patients than of healthy subjects and dramatically elevated in RA synovial fluids compared to RA serums. Immunohistochemistry reveals that synoviolin+ fibroblast-like synoviocytes and CD68+ macrophage-like synoviocytes are the main IL-26-producing cells in RA joints. Fibroblast-like synoviocytes from RA patients constitutively produce IL-26 and this production is upregulated by IL-1-beta and IL-17A. We have therefore investigated the role of IL-26 in the inflammatory process. Results show that IL-26 induces the production of the proinflammatory cytokines IL-1-beta, IL-6, and tumor necrosis factor (TNF)-alpha by human monocytes and also upregulates the expression of numerous chemokines (mainly CCL20). Interestingly, IL-26-stimulated monocytes selectively promote the generation of RORgamma t+ Th17 cells, through IL-1-beta secretion by monocytes. More precisely, IL-26-stimulated monocytes switch non-Th17 committed (IL-23R− or CCR6− CD161−) CD4+ memory T cells into Th17 cells. Finally, synovial fluids from RA patients also induce Th17 cell generation and this effect is reduced after IL-26 depletion. These findings show that IL-26 is constitutively produced by RA synoviocytes, induces proinflammatory cytokine secretion by myeloid cells, and favors Th17 cell generation. IL-26 thereby appears as a novel proinflammatory cytokine, located upstream of the proinflammatory cascade, that may constitute a promising target to treat RA and chronic inflammatory disorders

Ab initio simulations of zeolite reactivity

The ab initio pseudopotential plane wave DFT simulation of the structure and properties of zeolite active sites and elementary catalytic reactions are discussed through the example of the protonation of water and the first step in the protolytic cracking mechanism of saturated hydrocarbons

Modeling proton-induced damage on 2-deoxy-D-ribose. Conformational analysis

International audienceModeling proton-induced damage in biological systems, in particular in DNA building blocks, is of major concern in studies on cancer proton therapy. This is indeed an extremely complex process and analysis of the mechanism at the molecular level is of crucial interest. Such collision reactions of protons on biological targets induce different reactions: excitation and ionization of the biomolecule, fragmentation of the ionized species, and charge transfer from the projectile ion toward the biomolecular target. In order to have an insight into such mechanisms, we have performed a theoretical approach of two of the most important steps, the fragmentation and the charge transfer processes. For that purpose, we have considered collision of protons with isolated 2-deoxy-D-ribose by means of ab-initio molecular dynamics and quantum chemistry molecular methods. The conformation of the sugar moiety has been analyzed and appears to induce important effects, in particular different fragmentation patterns have been pointed out with regard to the conformation, and significant variations of the charge transfer cross sections have been exhibited