Kopp, Andrea and Bala, Margarita and Buechler, Christa and Falk, Werner and Gross, Philipp and Neumeier, Markus and Schoelmerich, Juergen and Schaeffler, Andreas (2010) C1q/TNF-Related Protein-3 Represents a Novel and Endogenous Lipopolysaccharide Antagonist of the Adipose Tissue. ENDOCRINOLOGY, 151 (11). pp. 5267-5278. ISSN 0013-7227,
Full text not available from this repository. (Request a copy)Abstract
Proteins secreted by adipocytes (adipokines) play an important role in the pathophysiology of type 2 diabetes mellitus and the associated chronic and low-grade state of inflammation. It was the aim to characterize the antiinflammatory potential of the new adipocytokine, C1q/TNF-related protein-3 (CTRP-3), which shows structural homologies to the pleiotropic adipocytokine adiponectin. mRNA and protein expression of CTRP-3 was analyzed by RT-PCR and Western blot. Recombinant CTRP-3 and small interfering RNA-based strategies were used to investigate the effect of CTRP-3 on toll-like receptor (TLR) ligand, lipopolysaccharide (LPS)-, and lauric acid-induced chemokine release of monocytes and adipocytes. Together with complex ELISA-based techniques, a designed TLR4/myeloid differentiation protein-2 fusion molecule shown to bind LPS was used to prove the ability of CTRP-3 to act as endogenous LPS antagonist. CTRP-3 is synthesized in monocytes and adipocytes. The recombinant protein dose-dependently inhibits the release of chemokines in monocytes and adipocytes that were induced by lauric acid, LPS, and other TLR ligands in vitro and ex vivo. CTRP-3 inhibits monocyte chemoattractant protein-1 release in adipocytes, whereas small interfering RNA-mediated knockdown of CTRP-3 up-regulates monocyte chemoattractant protein-1 release, reduces lipid droplet size, and decreases intracellular triglyceride concentration in adipocytes, causing a dedifferentiation into a more proinflammatory and immature phenotype. By using a designed TLR4/MD-2 fusion molecule, it is shown by different techniques that CTRP-3 specifically and effectively inhibits the binding of LPS to its receptor, TLR4/MD-2. CTRP-3 inhibits three basic and common proinflammatory pathways involved in obesity and type 2 diabetes mellitus (adipo-inflammation) by acting as an endogenous LPS antagonist of the adipose tissue. (Endocrinology 151: 5267-5278, 2010)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REPEAT-CONTAINING SEQUENCE; TUMOR-NECROSIS-FACTOR; TOLL-LIKE RECEPTORS; INSULIN-RESISTANCE; COLLAGENOUS REPEAT; INNATE IMMUNITY; 26-KDA PROTEIN; CELL-LINE; TRANSCRIPTIONAL REGULATION; CHROMOSOMAL LOCALIZATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jul 2020 06:39 |
| Last Modified: | 07 Jul 2020 06:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/23925 |
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