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APPETITE, OBESITY AND METABOLISM

Interleukin-6 and interleukin-15 are selectively regulated by lipopolysaccharide and interferon- in primary pig adipocytes

Department of Animal Sciences, Comparative Medicine Program, Purdue University, West Lafayette, Indiana 47907-2054

Submitted 7 October 2003 ; accepted in final form 27 November 2003

3T3-L1 adipocytes express the lipopolysaccharide (LPS) receptor and respond to direct stimulation with the antigen by increasing the expression of inflammatory mediators. Activation of this receptor by its ligand in the macrophage causes the activation and translocation of nuclear factor-B (NF-B) to the nucleus where it regulates the expression of proinflammatory cytokines and other target genes. We investigated whether LPS could stimulate NF-B translocation in primary pig adipocytes and regulate the expression and secretion of TNF- and IL-6. LPS clearly induced the nuclear translocation of NF-B and also upregulated (P < 0.05) the mRNA expression and secretion of IL-6 into the culture medium. An induction of TNF- expression by LPS was not detected, but with extended incubation (8 h), there was a modest increase (P < 0.09) in the media concentration of this cytokine. Inhibition of either ERK1/2, PKC, or the inhibitory G protein (G_i) with U-0126, bisindolylmaleimide HCl, and pertussis toxin, respectively, blocked (P < 0.05) the increase in IL-6 expression caused by LPS. Because LPS administration in vivo increases circulating concentrations of IFN-, and because this cytokine also regulates multiple immune modulators in the adipocyte, we also determined whether IFN- regulates cytokine expression in primary adipocytes. Although the expression of IL-6 and TNF- was unresponsive to IFN-, the expression of IL-15 was markedly upregulated (P < 0.01). Furthermore, the induction of IL-15 expression by IFN- was blocked by inhibition of PKC. These data indicate that NF-B is responsive to LPS in the adipocyte and also identify key mediators of LPS-induced IL-6 expression. In addition, we provide novel evidence that IFN- targets the adipocyte to induce IL-15 expression, thus indicating a possible role for the adipocyte in the regulation of T-cell function and muscle metabolism during the innate immune response.

adipocyte; interleukin; interferon

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