Adiponectin differentially regulates cytokines in porcine macrophages

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Abstract

Adiponectin, an adipocyte-derived hormone, attenuates the production of TNFα by activated human macrophages. In the present study, we used porcine blood-derived macrophages to test the hypothesis that the anti-inflammatory action of adiponectin includes suppression of IL6 and an induction of IL10. Adiponectin suppressed both TNFα and IL6 production in macrophages activated with lipopolysaccharide (P<0.01). In contrast, adiponectin increased IL10 expression (P<0.05) and augmented (P<0.05) the induction of this cytokine by lipopolysaccharide (LPS). Mechanistically, the attenuation of proinflammatory cytokine production by adiponectin was associated with an attenuation of the translocation of NFκB to the nucleus. Either adiponectin or inhibition of ERK1/2 with U0126 diminished the induction of IL6 by LPS (P<0.05), but the combination of adiponectin and the inhibitor did not further reduce IL6 production. In contrast, the inhibitory actions of adiponectin and a p38 MAPK inhibitor (SB203580) were additive (P<0.05). These data indicate that the anti-inflammatory actions of adiponectin include suppression of IL6 and induction of IL10. In addition, we provide evidence that some of the anti-inflammatory actions of adiponectin are mediated in part by suppression of NFκB signaling and ERK1/2 activity.

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Materials and methods

Porcine blood-derived macrophage isolation and culture. Blood collected from barrows at slaughter (666 mL) into Alsever’s solution (334 mL) was centrifuged in 50 mL conical tubes at 900g for 20 min at 20 °C. The buffy coats from five conicals of blood were mixed in a new conical with 30 mL Hanks’ balanced salt solution (HBSS) at pH 7.4 (Gibco-BRL, Grand Island, NY). Twenty microliters of the buffy coat plus HBSS mixture was layered atop 15 mL of Ficoll–Paque (Sigma Chemicals, St. Louis, MO) in a

Adiponectin regulates TNFα and IL6 in porcine blood-derived macrophages

The regulation of TNFα and IL6 release by macrophages pretreated with adiponectin for 24 h prior to exposure to LPS for an additional 24 h is presented in Figs. 1A and B, respectively. Adiponectin at 10 μg/mL was sufficient to suppress cytokine release by approximately 50% (P<0.05). Similar results were obtained for IL6 in that 10 μg/mL adiponectin abrogated (P<0.05) the LPS response in macrophages. These findings confirm the findings of Yokota et al. [2] and extend the anti-inflammatory activity

Conclusions

In conclusion, we have confirmed that adiponectin attenuates the LPS-induced expression and release of TNFα from macrophages, and show for the first time that this hormone also down-regulates IL6 while up-regulating IL10. Furthermore, we provided solid evidence that the anti-inflammatory activity of adiponectin is achieved in part by inhibition of NFκB activation and suppression of ERK1/2 activity. Collectively, these data substantiate the potential therapeutic benefit of adiponectin in the

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