CD14 protein as a modulator of the inflammatory response / Bialko CD14 jako modulator odpowiedzi zapalnej.

CD14 is one of the key proteins involved in the activation of the inflammatory response of immune cells. CD14 binds bacterial lipopolysaccharide (LPS) and transfers its molecules to the complex of Toll-like receptor 4 (TLR4) and MD-2 protein, which in turn triggers pro-inflammatory signaling pathways necessary to combat infection. CD14 determines the final shape of the pro-inflammatory reaction of cells to LPS, serving as a transporter of this endotoxin and also as a regulator of TLR4 activity. In addition, CD14 transports other molecules of microbial or endogenous origin to their target receptors/proteins, participating in the activation of pro-inflammatory signaling pathways triggered by the presence of pathogens, as well as tissue damage. Currently, more attention is paid to the role of the CD14 protein in the development of non-infectious diseases such as autoimmune diseases, metabolic diseases and cardiovascular diseases.

Flotillins affect LPS-induced TLR4 signaling by modulating the trafficking and abundance of CD14.

Lipopolysaccharide (LPS) induces a strong pro-inflammatory reaction of macrophages upon activation of Toll-like receptor 4 (TLR4) with the assistance of CD14 protein. Considering a key role of plasma membrane rafts in CD14 and TLR4 activity and the significant impact exerted on that activity by endocytosis and intracellular trafficking of the both LPS acceptors, it seemed likely that the pro-inflammatory reaction could be modulated by flotillins. Flotillin-1 and -2 are scaffolding proteins associated with the plasma membrane and also with endo-membranes, affecting both the plasma membrane dynamics and intracellular protein trafficking. To verify the above hypothesis, a set of shRNA was used to down-regulate flotillin-2 in Raw264 cells, which were found to also become deficient in flotillin-1. The flotillin deficiency inhibited strongly the TRIF-dependent endosomal signaling of LPS-activated TLR4, and to a lower extent also the MyD88-dependent one, without affecting the cellular level of TLR4. The flotillin depletion also inhibited the pro-inflammatory activity of TLR2/TLR1 and TLR2/TLR6 but not TLR3. In agreement with those effects, the depletion of flotillins down-regulated the CD14 mRNA level and the cellular content of CD14 protein, and also inhibited constitutive CD14 endocytosis thereby facilitating its shedding. Ultimately, the cell-surface level of CD14 was markedly diminished. Concomitantly, CD14 recycling was enhanced via EEA1-positive early endosomes and golgin-97-positive trans-Golgi network, likely to compensate for the depletion of the cell-surface CD14. We propose that the paucity of surface CD14 is the reason for the down-regulated signaling of TLR4 and the other TLRs depending on CD14 for ligand binding.

Mechanical Recycling and Its Effects on the Physical and Mechanical Properties of Polyamides.

The aim of this study is to investigate the impact of mechanical recycling on the physical and mechanical properties of recycled polyamide 6 (PA6) and polyamide 66 (PA66) in relation to their microstructures. Both PA6 and PA66 raw materials were reprocessed six times, and the changes in their properties were investigated as a function of recycling number. Until the sixth round of recycling, slight changes in the mechanical properties were detected, except for the percentage of elongation. For the physical properties, the change in both flexural strength and Young's modulus followed a decreasing trend, while the trend in terms of elongation showed an increase. Microscopic analysis was performed on virgin and recycled specimens, showing that imperfections in the crystalline regions of polyamide 6 increased as the number of cycles increased.