Unraveling mechanisms of pentraxin 3 secretion in adipocytes during inflammation.

Abstract

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor playing an important role in immune response and inflammation. Lipopolysaccharide (LPS) stimulation can significantly induce PTX3 expression and secretion in adipocytes. Appropriate regulation of PTX3 secretion is critical for inflammatory homeostasis. Using chemical inhibitors of conventional and unconventional protein secretion, we explored the mechanisms that control LPS-stimulated PTX3 secretion in 3T3-L1 adipocytes. Inhibiting the conventional protein secretion blocked LPS-stimulated PTX3 secretion, resulting in cellular PTX3 accumulation in adipocytes. We also detected PTX3 in exosomes from LPS-treated adipocytes; inhibiting exosome trafficking attenuated PTX3 secretion. However, only 4.3% of secreted PTX3 was detected in exosomes compared to 95.7% in the non-exosomal fractions. The fractionation of isolated exosomes by the iodixanol density gradient centrifugation confirmed that a small portion of secreted PTX3 overlapped with exosomal markers in small extracellular-vesicle fractions. We conclude that PTX3 is secreted mainly through conventional protein secretion, and a small percentage of PTX3 is released in exosomes from LPS-stimulated adipocytes.

• Authors: Te-Yueh Lin, Hong Guo, Xiaoli Chen
• Journal: Journal of molecular endocrinology (J Mol Endocrinol) Vol. 67 Issue 3 Pg. 55-69 (07 26 2021) ISSN: 1479-6813 [Electronic] England
• PMID: 34213423 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Endosomal Sorting Complexes Required for Transport
• Lipopolysaccharides
• Protein Sorting Signals
• Serum Amyloid P-Component
• PTX3 protein
• C-Reactive Protein

Topics

• 3T3-L1 Cells
• Adipocytes (drug effects, metabolism)
• Animals
• Biomarkers
• C-Reactive Protein (biosynthesis, chemistry, genetics)
• Cells, Cultured
• Endosomal Sorting Complexes Required for Transport (metabolism)
• Extracellular Vesicles (metabolism)
• Gene Expression Regulation
• Lipopolysaccharides (immunology, pharmacology)
• Macrophages (immunology, metabolism)
• Mice
• Mitochondria (genetics, metabolism)
• Panniculitis (etiology, metabolism)
• Protein Interaction Domains and Motifs
• Protein Sorting Signals
• Serum Amyloid P-Component (biosynthesis, chemistry, genetics)