Journal of Biological Chemistry
Volume 275, Issue 32, 11 August 2000, Pages 24255-24263
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MECHANISMS OF SIGNAL TRANSDUCTION
The Lipopolysaccharide-activated Toll-like Receptor (TLR)-4 Induces Synthesis of the Closely Related Receptor TLR-2 in Adipocytes*

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The central regulatory role of the adipocyte in whole body energy homeostasis is well established. However, recent findings suggest that preadipocytes and adipocytes may play an important physiological role in the regulation of both the innate and adaptive immune response. To systematically characterize the molecular machinery of the adipocyte that mediates the recognition of pathogens, we have focused our analysis on the recently identified Toll-like receptors (TLRs). These receptors have been implicated as mediators of the cellular response to bacterial lipopolysacharides (LPSs). Here, we report the cloning and functional characterization of mouse TLR-2 from 3T3-L1 adipocytes. TLR-2 synthesis is strongly induced in the adipocyte by LPS, TNFα, and the yeast cell wall extract zymosan. TLR-2 undergoes a lengthy intracellular maturation process with a half-life of exit from the ER of approximately 3 h. Furthermore, LPS treatment of adipocytes results in dramatic changes at the level of gene expression, including the synthesis of a distinct set of secretory proteins such as interleukin-6. Our studies demonstrate the presence of a fully intact pathway of innate immunity in the adipocyte that can be activated by LPS binding to the cell surface and results in the secretion of immunomodulatory molecules.

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Published, JBC Papers in Press, May 22, 2000, DOI 10.1074/jbc.M002137200

*

This work was supported by Juvenile Diabetes Foundation Fellowship 3-2000-176 (to Y. L.); Training Program in Cellular and Molecular Biology and Genetics Grant T32-GM07491 (to A. H. B. and H. L.); grants from the American Diabetes Association (to P. E. S.); NIDDK, National Institutes of Health (NIH), Grant 1R01-DK55758 (to P. E. S.); a grant from the G. Harold and Leila Y. Mathers foundation (to M. P. L. and P. E. S.); NCI, NIH, Grant R01-CA-80250 (to M. P. L.); and grants from the Charles E. Culpeper Foundation (to M. P. L.) and the Sidney Kimmel Foundation for Cancer Research (to M. P. L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AF165189.