Emerging roles of angiopoietin-like proteins in inflammation: Mechanisms and potential as pharmacological targets.

Angiopoietin-like proteins (ANGPTLs), a family of eight secreted glycoproteins termed ANGTPL1-8, are involved in angiogenesis, lipid metabolism, cancer progression, and inflammation. Their roles in regulating lipid metabolism have been intensively studied, as some ANGPTLs are promising pharmacological targets for hypertriglyceridemia and associated cardiovascular disease. Recently, the emerging roles of ANGPTLs in inflammation have attracted great attention. First, elevated levels of multiple circulating ANGPTLs in inflammatory diseases make them potential disease biomarkers. Second, multiple ANGPTLs regulate acute or chronic inflammation via various mechanisms, including triggering inflammatory signaling through their action as ligands for integrin or forming homo- /hetero-oligomers to regulate signal transduction via extra- or intracellular mechanisms. As dysregulation of the inflammatory response is a critical trigger in many diseases, understanding the roles of ANGPTLs in inflammation will aid in drug/therapy development. Here, we summarize the roles, mechanisms, and potential therapeutic values for ANGPTLs in inflammation and inflammatory diseases.

ANGPTL3 negatively regulates IL-1ß-induced NF-κB activation by inhibiting the IL1R1-associated signaling complex assembly.

Interleukin-1ß (IL-1ß)-induced signaling is one of the most important pathways in regulating inflammation and immunity. The assembly of the receptor complex, consisting of the ligand IL-1ß, the IL-1 receptor (IL-1R) type 1 (IL1R1), and the IL-1R accessory protein (IL1RAP), initiates this signaling. However, how the IL1R1-associated complex is regulated remains elusive. Angiopoietin like 3 (ANGPTL3), a key inhibitor of plasma triglyceride clearance, is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms. Presently, ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases. However, most studies have focused on the secreted form of ANGPTL3, while its intracellular role is still largely unknown. Here, we report that intracellular ANGPTL3 acts as a negative regulator of IL-1ß-triggered signaling. Overexpression of ANGPTL3 inhibited IL-1ß-induced NF-κB activation and the transcription of inflammatory genes in HepG2, THP1, and HEK293T cells, while knockdown or knockout of ANGPTL3 resulted in opposite effects. Mechanistically, ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain (FLD) and disrupted the assembly of the IL1R1-associated complex. Taken together, our study reveals a novel role for ANGPTL3 in inflammation, whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver.

Spaceflight-associated neuro-ocular syndrome: a review of potential pathogenesis and intervention.

With the continuing progress in space exploration, a new and perplexing condition related to spaceflight ocular syndrome has emerged in the past four decades. National Aeronautics and Space Administration (NASA) has named this condition "spaceflight-associated neuro-ocular syndrome" (SANS). This article gives an overview of the current research about SANS and traditional Chinese medicine (TCM) by analyzing the existing publications on PubMed and CNKI and reports from NASA about SANS, summarizing the potential pathogenesis of SANS and physical interventions for treating SANS, and discussing the feasibility of treating SANS with TCM. Due to the unique characteristics of the space environment, it is infeasible to conduct large-scale human studies of SANS. SANS may be the result of the interaction of multiple factors, including inflammation and fluid displacement in the optic nerve sheath and cerebrospinal fluid. We should pay attention to SANS. Visual function is not only related to the health of astronauts but also closely related to space operations. TCM has antioxidative stress and antiapoptotic effects and is widely used for optic nerve diseases. TCM has great potential to prevent SANS.