Aryl hydrocarbon receptor activation alters immune cell populations in the lung and bone marrow during coronavirus infection.

Respiratory viral infections are one of the major causes of illness and death worldwide. Symptoms associated with respiratory infections can range from mild to severe, and there is limited understanding of why there is large variation in severity. Environmental exposures are a potential causative factor.

Exposure to a mixture of 23 chemicals associated with unconventional oil and gas operations alters immune response to challenge in adult mice.

The prevalence of unconventional oil and gas (UOG) operations raises concerns regarding the potential for adverse health outcomes following exposure to water tainted by mixtures of UOG associated chemicals. The potential effects that exposure to complex chemical mixtures has on the immune system have yet to be fully evaluated. In this study, effects on the immune system of adult mice exposed to a mixture of 23 chemicals that have been associated with water near active UOG operations were investigated.

The Ancestral Environment Shapes Antiviral CD8 T cell Responses across Generations.

Recent studies have linked health fates of children to environmental exposures of their great grandparents. However, few studies have considered whether ancestral exposures influence immune function across generations. Here, we report transgenerational inheritance of altered T cell responses resulting from maternal (F0) exposure to the aryl hydrocarbon receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Developmental Exposure to a Mixture of 23 Chemicals Associated With Unconventional Oil and Gas Operations Alters the Immune System of Mice.

Chemicals used in unconventional oil and gas (UOG) operations have the potential to cause adverse biological effects, but this has not been thoroughly evaluated. A notable knowledge gap is their impact on development and function of the immune system. Herein, we report an investigation of whether developmental exposure to a mixture of chemicals associated with UOG operations affects the development and function of the immune system.

Insulin dependent apolipoprotein B degradation and phosphatidylinositide 3-kinase activation with microsomal translocation are restored in McArdle RH7777 cells following serum deprivation.

Previous studies in rat hepatocytes demonstrated that insulin-dependent apolipoprotein (apo) B degradation (IDAD) is lost when cells are maintained for 3 d under enriched culture conditions. Loss of IDAD correlates with increased expression of protein tyrosine phosphatase 1B (PTP1B) known to be associated with resistance to insulin signaling in the liver. McArdle RH7777 hepatoma (McA) cells cultured in serum containing medium are resistant to IDAD; demonstrate a 30% increase in apo B secretion, and express increased levels of PTP1B protein and mRNA.

Insulin-dependent apolipoprotein B degradation is mediated by autophagy and involves class I and class III phosphatidylinositide 3-kinases.

Insulin acutely stimulates the degradation of apolipoprotein B (apo B) which decreases very low density lipoprotein (VLDL) secretion by liver. Insulin-dependent apo B degradation (IDAD) occurs following phosphatidylinositide 3-kinase (PI3K) activation and involves lysosomal degradation. Insulin suppression of apo B secretion is blocked by over-expression of phosphatase and tensin homologue (PTEN) in McArdle RH7777 (McA) cells suggesting the importance of Class I PI3K generated PI (3,4,5) triphosphate (PIP3) in IDAD.

Insulin suppression of apolipoprotein B in McArdle RH7777 cells involves increased sortilin 1 interaction and lysosomal targeting.

Insulin suppresses secretion of very low density lipoprotein (VLDL) apolipoprotein (apo) B in primary rodent hepatocytes (RH) by favoring the degradation of B100, the larger form of apo B, through post-endoplasmic reticulum proteolysis. Sortilin 1 (sort1), a multi-ligand sorting receptor, has been proposed as a mediator of lysosomal B100 degradation by directing B100 in pre-VLDL to lysosomes rather than allowing maturation to VLDL and secretion. The purpose of our studies was to investigate the role of sort1 in insulin-dependent degradation of apo B.

Acute suppression of apo B secretion by insulin occurs independently of MTP.

Secretion of apolipoprotein (apo) B-containing lipoproteins by the liver depends mainly upon apo B availability and microsomal triglyceride transfer protein (MTP) activity and is subject to insulin regulation. Hepatic MTP mRNA expression is negatively regulated by insulin which correlates with inhibition of apo B secretion suggesting that insulin might suppress apo B secretion through an MTP-dependent mechanism. To investigate this possibility, we examined the acute effect of insulin on hepatic MTP expression and activity levels in vivo utilizing apobec-1(-/-) mice.