TNF-α Levels In Macrophages Research Articles

Understanding the pathogenesis of engineered stone-associated silicosis: The effect of particle chemistry on the lung cell response.

The resurgence of severe and progressive silicosis among engineered stone benchtop industry workers is a global health crisis. We investigated the link between the physico-chemical characteristics of engineered stone dust and lung cell responses to understand components that pose the greatest risk. Respirable dust from 50 resin-based engineered stones, 3 natural stones and 2 non-resin-based materials was generated and analysed for mineralogy, morphology, metals, resin, particle size and charge. Human alveolar epithelial cells and macrophages were exposed in vitro to dust and assessed for cytotoxicity and inflammation. Principal component analysis and stepwise linear regression were used to explore the relationship between engineered stone components and the cellular response. Cutting engineered stone generated fine particles of <600 nm. Crystalline silica was the main component with metal elements such as Ti, Cu, Co and Fe also present. There was some evidence to suggest differences in cytotoxicity (p = 0.061) and IL-6 (p = 0.084) between dust samples. However, IL-8 (CXCL8) and TNF-α levels in macrophages were clearly variable (p < 0.05). Quartz explained 11% of the variance (p = 0.019) in macrophage inflammation while Co and Al accounted for 32% of the variance (p < 0.001) in macrophage toxicity, suggesting that crystalline silica only partly explains the cell response. Two of the reduced-silica, non-engineered stone products induced considerable inflammation in macrophages. These data suggest that silica is not the only component of concern in these products, highlighting the caution required as alternative materials are produced in an effort to reduce disease risk.

Mannose-coated nanozyme for relief from chemotherapy-induced peripheral neuropathic pain

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a progressive and disturbing peripheral neuropathy with currently no effective treatment. Aberrant production of reactive oxygen species (ROS) in macrophages near peripheral nerves plays a dominant role in CIPNP; however, traditional ROS scavengers have difficulty maintaining viability to target macrophages invivo. Mannose-coated superparamagnetic iron oxide nanoparticles (mSPIONs) were synthesized to treat CIPNP. The anti-ROS and anti-inflammatory effects of mSPIONs were assessed in J774A.1 cells and sciatic nerves in a nociception mouse model induced with vincristine (VCR). We found that the mSPIONs significantly reduced ROS levels invitro and invivo. Furthermore, mSPIONs administration specifically reduced IL-6 and TNF-α levels in macrophages near the sciatic nerve and relieved VCR-induced peripheral neuropathic pain. Inhibition of the VCR-upregulated HIF1α/NF-κB signaling pathway may be involved in the alleviation of inflammation. These results provide a new approach for relieving CIPNP using a nanozyme.

Oxidative Stress Modulates KLF6Full and Its Splice Variants

Induction of reactive oxygen species (ROS) is a central mechanism in alcohol hepatotoxicity. Krüppel-like factor 6 (KLF6), a transcription factor and a tumor-suppressor gene, is an early-responsive gene to injury; however, the effect of ROS and alcohol on KLF6 induction is unknown. The aim of this study is to investigate the contribution of 2 sources of ROS, cytochrome P450 2E1 (CYP2E1), NAD(P)H quinone oxidoreductase (NQO1), and alcohol on the modulation of KLF6(Full) expression, splicing to KLF6_V1 and KLF6_V2, and the effect on TNFα, a downstream target. Endogenous ROS production in CYP2E1-expressing HepG2 cells induced mRNA and protein expression of KLF6(Full) and its splice variants compared to control cells. Incubation with pro-oxidants such as arachidonic acid (AA), β-naphtoflavone, and H(2) O(2) further enhanced KLF6(Full) and its splice variants. The AA effects on KLF6(Full) and its splice forms were blocked by vitamin E-which prevents lipid peroxidation-and by diallylsulfide-a CYP2E1 inhibitor. Menadione and paraquat, 2 pro-oxidants metabolized via NQO1, induced KLF6(Full) mRNA in a thiol-dependent manner. Antioxidants and an NQO1 inhibitor suppressed the menadione-dependent increase in KLF6(Full) and its splice variants mRNA. Furthermore, primary hepatocytes and livers from chronic alcohol-fed rats, with elevated lipid peroxidation, H(2) O(2) and CYP2E1 but with low GSH, showed a ~2-fold increase in KLF6(Full) mRNA compared to controls. Inhibition of p38 phosphorylation further up-regulated the CYP2E1 and the AA effects on KLF6(Full) mRNA, whereas inhibition JNK and ERK1/2 phosphorylation decreased both. KLF6_V1 but not KLF6(Full) ablation markedly increased TNFα levels in macrophages; thus, TNFα emerges as a downstream target of KLF6_V1. The novel effect of ROS on modulating KLF6(Full) expression and its splice variants could play a relevant role in liver injury and in TNFα regulation.

Preventive and Therapeutic Effects Ramulus Mori Extract on Collagen-Induced Arthritis in Mice via Suppression of Inflammatory T Cells

We researched the preventive and therapeutic activities of the extract of Ramulus Mori (ERM) to observe its effects on collagen-induced arthritis (CIA) in mice and to explore the mechanisms of ERM in the treatment of rheumatoid arthritis (RA). We examined the in vitro levels of tumor necrosis factor α (TNF-α) released in macrophages and of interferon (IFN)-γ and interleukin (IL)-4 released in splenocytes. For in vivo experiments, we randomly divided 24 mice into four groups, after type II collagen (CII) injections and at euthanization. The levels of plasma cytokines (TNF-α, IL-6, IL-17), rheumatoid factor (RF; IgG, IgM), and anti-CII antibody were measured using ELISA kits. The number of immunocytes (CD4+ T cells, CD3+/CD69+ T cells, B220+/CD45+ B cells, CD11b+/Gr-1+ cells) relative to RA was calculated using flow cytometry (FACS). The articular index (AI) was recorded once a week for 4 weeks. Sections of tissues from the knee joints were stained with hematoxylin and eosin (H&E) and Masson trichrome (MT) after the mice with CIA were euthanized. ERM reduced the levels of TNF-α in macrophages and IFN-γ in spleen cells, decreased AI scores, and improved inflammation of paw joints (PJ). ERM also suppressed the number of immunocytes in peripheral blood mononuclear cells (PBMCs) and PJ, and reduced the levels of cytokines (TNF-α, IL-6, and IL-17), RF, and anti-CII antibody in the sera. TNF-α and Th1 cells play very important roles in the formation and development of RA. ERM and methotrexate notably decreased the induction of RA in the CIA mice model by reducing the levels of inflammatory cytokines and RF in the sera and suppressing the number of immunocytes among PBMCs and PJ.