[The two sides of ADAM17 in inflammation: implications in atherosclerosis and obesity]

Area of Science:

• Biochemistry
• Molecular Biology
• Immunology

Background:

• ADAM17, also known as TNF Alpha Converting Enzyme (TACE), is a key metalloproteinase.
• It mediates the shedding of over 40 transmembrane proteins, including cytokines, growth factors, and receptors.
• ADAM17's function is critical in cellular inflammatory processes.

Purpose of the Study:

• To investigate the multifaceted role of ADAM17 in regulating inflammation.
• To explore ADAM17's involvement in various inflammation-driven pathologies.
• To highlight ADAM17 as a potential therapeutic target.

Main Methods:

• Utilizing cell-based assays with ADAM17-deficient cells or mutated substrates.
• Employing genetically modified mouse models, including conditional knock-outs and overexpression of uncleavable substrates.
• Analyzing the impact of ADAM17 activity on inflammatory pathways and disease models.

Main Results:

• ADAM17 activity can have opposing effects on inflammation due to its diverse substrate cleavage.
• Evidence supports ADAM17's involvement in atherosclerosis, adipose tissue metabolism, insulin resistance, and diabetes.
• In vivo studies using conditional knock-out mice confirm ADAM17's regulatory role in inflammation.

Conclusions:

• ADAM17 is a critical regulator of inflammatory processes with significant implications for metabolic and cardiovascular diseases.
• The broad substrate specificity of ADAM17 underscores its importance in complex pathologies.
• Further research into ADAM17 function may yield novel therapeutic strategies for inflammation-driven diseases.