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Anti-inflammatory activity of a globular adiponectin function on RAW 264 cells stimulated by lipopolysaccharide from Aggregatibacter actinomycetemcomitans

Department of Preventive Dentistry, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
FEMS Immunology & Medical Microbiology (Impact Factor: 2.55). 06/2009; 56(3):241-7. DOI: 10.1111/j.1574-695X.2009.00573.x
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ABSTRACT Adiponectin is an adipokine with potent anti-inflammatory properties. We previously reported that a globular adiponectin (gAd) suppresses Aggregatibacter actinomycetemcomitans lipopolysaccharide-induced nuclear factor-kappaB activity, suggesting an anti-inflammatory effect of gAd. In this study, we investigated whether gAd is able to modulate the effect of A. actinomycetemcomitans lipopolysaccharide on cytokine induction in a murine macrophage cell line (RAW 264). The phosphorylation of p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and IkappaB kinase alpha/beta and the degradation of IkappaB, which were induced by A. actinomycetemcomitans lipopolysaccharide intoxication, were clearly reduced in gAd-pretreated RAW 264 cells compared with the untreated cells. Expression levels of tumor necrosis factor (TNF)-alpha and interleukin-10 (IL-10) mRNA were assessed by real-time PCR. Cell-free supernatants were collected after 12 h of stimulation and analyzed by enzyme-linked immunosorbent assay for TNF-alpha and IL-10. Pretreatment with gAd significantly inhibited the A. actinomycetemcomitans lipopolysaccharide-induced TNF-alpha mRNA expression and protein secretion. In contrast, pretreatment with gAd significantly enhanced the A. actinomycetemcomitans lipopolysaccharide-induced IL-10 mRNA expression and protein secretion. These data suggest a mechanism for the anti-inflammatory activity of gAd in local inflammatory lesions, such as periodontitis.

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Available from: Kazuaki Nonaka, Jan 27, 2015
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    • "Adiponectin reduced significantly the constitutive TNFα expression. A number of studies have shown that adiponectin counteracts the stimulatory effects of periodontopathogens or IL-1β on the expression of proinflammatory cytokines in periodontal cells [40, 65, 70]. Therefore, our findings are in line with these studies and emphasize the anti-inflammatory characteristics of this adipokine. "
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    • "Both anti-inflammatory actions and proinflammatory mechanisms have been described with reference to gAd. Recently, Kamio et al showed that gAd pretreatment of RAW264 cells significantly inhibited lipopolysaccharide-induced tumor necrosis factor alpha (TNF-α) expression and enhanced the expression of interleukin 10.31 Whereas a study by Zhang et al showed that gAd suppresses TNF-α-induced ICAM-1 expression in vascular endothelial cells at concentrations higher than 1 μg/mL, the suppressive effect is lost at concentrations lower than 0.25 μg/mL.32 "
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    • "It has been proposed that amelioration of periodontitis by APT might cause an increase in serum levels of adiponectin in type 2 diabetic subjects [24]. Pretreatment of mice with gAd was shown to suppress Aggregatibacter actinomycetemcomitans LPS-induced TNFα expression in a murine macrophage cell line [25]. gAd was also found to suppress osteoclast formation induced by LPS of A. actinomycetemcomitans [26]. "
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