Journalartikel

Evidence of an anti-inflammatory toll-like receptor 9 (TLR 9) pathway in adipocytes


AutorenlisteThomalla, Miriam; Schmid, Andreas; Neumann, Elena; Pfefferle, Petra Ina; Mueller-Ladner, Ulf; Schaffler, Andreas; Karrasch, Thomas

Jahr der Veröffentlichung2019

Seiten325-343

ZeitschriftJournal of Endocrinology

Bandnummer240

Heftnummer2

ISSN0022-0795

eISSN1479-6805

Open Access StatusBronze

DOI Linkhttps://doi.org/10.1530/JOE-18-0326

VerlagBioScientifica


Abstract
Adipocytes express various pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and actively participate in anti-bacterial and anti-viral host defence. Obesity is associated with adipose tissue PRR expression. The potential role of Toll-like receptor 9 (TLR9) in adipocytes has not yet been investigated. Here, we evaluated TLR9 expression during adipocyte differentiation (AD) of 3T3-L1 adipocytes, in primary murine adipocytes and in different murine and human adipose tissue depots by real-time PCR, immunocytochemistry and immunohistochemistry. TLR9 expression was inhibited using specific siRNA-mediated knockdown, and TLR9 signaling was induced using specific class A, B and C agonistic CpG-oligodeoxynucleotide (ODN) treatment vs ODN controls in 3T3-L1 adipocytes and in primary murine adipocytes from Tlr9(wt/wt) vs Tlr9(-/-) mice. We found that TLR9 gene expression is induced during AD and that T LR9 protein is expressed in murine gonadal and human visceral adipocytes. AD depends on intact TLR9 expression. Tlr9(-/-) mice demonstrate significantly reduced adiponectin serum levels, while siRNAmediated TLR9 knockdown led to reduced adiponectin mRNA expression in adipocytes. TLR9 ligands (CpG-ODNs) inhibit pro-inflammatory resistin secretion in mature 3T3-L1 adipocytes. Tlr9(-/-) as compared to Tlr9wt/wt adipocytes exhibit increased resistin and MCP1 secretion and reduced adiponectin secretion into cell culture supernatants, while TLR9 ligands (ODNs) show differential effects in Tlr9(-/-) vs Tlr9(wt/wt) primary murine adipocytes. TLR9 expression is significantly increased in visceral compared to subcutaneous adipose tissue depots in non-diabetic obese patients and correlates with systemic resistin levels in a compartment-specific manner. Thus, adipocytic TLR9 is a putative, new protective factor during (obesity-associated) adipose tissue inflammation.



Zitierstile

Harvard-ZitierstilThomalla, M., Schmid, A., Neumann, E., Pfefferle, P., Mueller-Ladner, U., Schaffler, A., et al. (2019) Evidence of an anti-inflammatory toll-like receptor 9 (TLR 9) pathway in adipocytes, Journal of Endocrinology, 240(2), pp. 325-343. https://doi.org/10.1530/JOE-18-0326

APA-ZitierstilThomalla, M., Schmid, A., Neumann, E., Pfefferle, P., Mueller-Ladner, U., Schaffler, A., & Karrasch, T. (2019). Evidence of an anti-inflammatory toll-like receptor 9 (TLR 9) pathway in adipocytes. Journal of Endocrinology. 240(2), 325-343. https://doi.org/10.1530/JOE-18-0326



Schlagwörter


ADIPOSE-TISSUE INFLAMMATIONCpGpattern recognition receptorPATTERN-RECOGNITION RECEPTORSTLR9


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