Polymorphisms in TREX1 and susceptibility to HIV-1 infection.

TREX-1 is a restriction factor against HIV-1. The coding sequence of TREX1 gene was analysed in HIV+ subjects searching for genetic variations possibly associated with the susceptibility to HIV infection. The single nucleotide polymorphism rs3135945 was significantly associated with HIV infection, emphasizing the involvement of TREX-1 in the anti-HIV response.

A comparative analysis of serologic parameters and oxidative stress in osteoarthritis and rheumatoid arthritis: reply to Mishra and colleagues.

In chronic diseases such as rheumatoid arthritis and osteoarthritis, the progression of the disease is characterized by stress oxidative, inflammation, and elevated levels of cholesterol. In mevalonate kinase deficiency, an auto-inflammatory disease, the correlation between inflammation and cholesterol levels is opposite. The metabolic pathway that underlies the production of cholesterol is the mevalonate pathway; it is also essential for the biosynthesis of isoprenoids involved in the control of several cell functions. This divergence of cholesterol levels, associated with these two inflammatory disorders, is probably due to a different etiology, pathogenesis, and progression.

Bacterial LPS differently modulates inflammasome gene expression and IL-1ß secretion in trophoblast cells, decidual stromal cells, and decidual endothelial cells.

Three Nod-like receptors (NLR family, pyrin domain containing 1/NLRP1, NLR family, pyrin domain containing 3/NLRP3, NLR family, CARD domain containing 4/NLRC4) and the adaptor molecule PYD and CARD domain containing protein/PYCARD are involved in the assembling of multiprotein complexes known as inflammasomes, leading to caspase 1 activation and consequent interleukin (IL)-1ß secretion. Considering that inflammasomes are involved in sensing pathogens and in triggering inflammatory and immune response, we hypothesized that they could also act in the placenta as an efficient innate mechanism during pregnancy infections. For this reason the activation of inflammasome was tested in 3 human placental cell populations in the presence of a common gram-negative compound (lipopolysaccharide [LPS]). The transcription of NLRP1, NLRP3, NLRC4, PYCARD, CASP1, and IL1B genes and the secretion of IL-1ß were evaluated in human first trimester cytotrophoblasts (CTBs), decidual stromal cells (DSCs), and endothelial cells (DECs) stimulated with LPS. In CTBs and DSCs, LPS induced an augmented expression of CASP1 and IL1B and the specific upregulation of NLRP3 within the 3 NLRs tested. Moreover, LPS induced secretion of IL-1ß from CTBs and DSCs. These results suggest the involvement of NLRP3 inflammasome in the placental innate response. The LPS did not affect inflammasome gene transcription and IL-1ß production in DECs. Bacterial LPS enhances NLRP3 inflammasome components in trophoblast and DSCs, suggesting that this innate immune complex could play a key role in placental immune defense.