Schmid, Andreas and Hochberg, Alexandra and Kreiss, Anja Franziska and Gehl, Jonas and Patz, Marissa and Thomalla, Miriam and Hanses, Frank and Karrasch, Thomas and Schaeffler, Andreas (2020) Role of progranulin in adipose tissue innate immunity. CYTOKINE, 125: 154796. ISSN 1043-4666, 1096-0023
Full text not available from this repository. (Request a copy)Abstract
Regulation of progranulin in adipocytes and its role in inflammation is poorly understood. Aim: (i) to investigate regulation of progranulin in adipocyte differentiation and adipose tissue compartments, (ii) to address progranulin expression in two murine (C57BL/6) models of inflammation. Results: Progranulin expression was induced during adipocyte differentiation. Neither estradiol nor testosterone or metabolic stimuli such as glucose and insulin modified progranulin synthesis. Fatty acids, bile acids and incretins GLP-1 and GIP-1 exerted potent and differential effects on progranulin secretion. LPS, TNF and IL6 significantly increased progranulin secretion. TLR9 agonists decreased and TLR1/2, TLR3, TLR5, and TLR2/6 ligands increased progranulin expression. TLR3-mediated progranulin induction was abrogated by inhibitors of NF-kappa B and PI3K pathways. Progranulin expression between murine epididymal and subcutaneous adipose tissue did not differ in total adipose tissue, in isolated adipocytes or in the stromal-vascular cell fraction (SVC). However, SVC expressed significantly higher levels of progranulin than adipocytes at all sites. In adipocytes, female mice had significantly higher progranulin expression at all sites. An intra-peritoneal LPS challenge in mice did not affect adipose tissue progranulin expression, whereas peritoneal infection by S. aureus increased progranulin expression after 24 h. Conclusions: There are relevant sex-, site- and cell-specific effects on progranulin gene expression that is induced during adipocyte differentiation and modulated by various inflammatory and metabolic factors. Most importantly, ligands for TLR1/2 and TLR2/6 (recognizing S. aureus) in vitro and infection by S. aureus in vivo induce progranulin expression suggesting a role of adipocytes in protection against infection by gram-positive bacteria.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR PROGRANULIN; INSULIN-RESISTANCE; CELL-LINE; INFLAMMATION; ADIPOKINE; OBESITY; PHOSPHORYLATION; DIFFERENTIATION; DYSLIPIDEMIA; EXPRESSION; Adipose tissue; Adipocyte; Adipokine; Toll-like receptor; S. aureus |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2021 06:52 |
| Last Modified: | 09 Apr 2021 06:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45561 |
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