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HDAC6 deacetylase activity is critical for lipopolysaccharide-induced activation of macrophages.

Yan B, Xie S, Liu Z, Ran J, Li Y, Wang J, Yang Y, Zhou J, Li D, Liu M - PLoS ONE (2014)

Bottom Line: However, the molecular mechanisms of how macrophages are activated are not fully understood.Our data show that suppression of HDAC6 activity significantly restrains LPS-induced activation of macrophages and production of pro-inflammatory cytokines.Further study reveals that the regulation of macrophage activation by HDAC6 is independent of F-actin polymerization and filopodium formation; instead, it is mediated by the effects of HDAC6 on cell adhesion and microtubule acetylation.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.

ABSTRACT
Activated macrophages play an important role in both innate and adaptive immune responses, and aberrant activation of macrophages often leads to inflammatory and immune disorders. However, the molecular mechanisms of how macrophages are activated are not fully understood. In this study, we identify a novel role for histone deacetylse 6 (HDAC6) in lipopolysaccharide (LPS)-induced macrophage activation. Our data show that suppression of HDAC6 activity significantly restrains LPS-induced activation of macrophages and production of pro-inflammatory cytokines. Further study reveals that the regulation of macrophage activation by HDAC6 is independent of F-actin polymerization and filopodium formation; instead, it is mediated by the effects of HDAC6 on cell adhesion and microtubule acetylation. These data thus suggest that HDAC6 is an important regulator of LPS-induced macrophage activation and might be a potential target for the management of inflammatory disorders.

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HDAC6 regulates LPS-induced M1 response.(A) RAW 264.7 cells pretreated with tubacin were stimulated with LPS (300 ng/ml) for 24 hours. The culture medium was then collected, and the concentrations of IL-6, TNF-α, and IL-10 were measured. (B) Primary BMMs pretreated with tubacin were stimulated with LPS (300 ng/ml) for 24 hours. The culture medium was then collected, and the concentrations of IL-6, TNF-α, and IL-10 were measured. ***, p<0.001; **, p<0.01; ns, not significant (p≥0.05).
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pone-0110718-g002: HDAC6 regulates LPS-induced M1 response.(A) RAW 264.7 cells pretreated with tubacin were stimulated with LPS (300 ng/ml) for 24 hours. The culture medium was then collected, and the concentrations of IL-6, TNF-α, and IL-10 were measured. (B) Primary BMMs pretreated with tubacin were stimulated with LPS (300 ng/ml) for 24 hours. The culture medium was then collected, and the concentrations of IL-6, TNF-α, and IL-10 were measured. ***, p<0.001; **, p<0.01; ns, not significant (p≥0.05).

Mentions: Next we investigated the role of HDAC6 in LPS-induced M1 response. RAW264.7 cells and primary BMMs pretreated with tubacin were stimulated with LPS for 24 hours. The pro-inflammatory cytokines IL-6 and TNF-α (M1 markers) and the anti-inflammatory cytokine IL-10 (M2 marker) were then assessed. We found that LPS-induced secretion of IL-6 and TNF-α was dramatically decreased by tubacin in both RAW264.7 cells and primary BMMs; by contrast, LPS-induced IL-10 production was not obviously affected by tubacin (Fig. 2A and 2B). These results suggest that HDAC6 is critical for LPS-induced M1 response.


HDAC6 deacetylase activity is critical for lipopolysaccharide-induced activation of macrophages.

Yan B, Xie S, Liu Z, Ran J, Li Y, Wang J, Yang Y, Zhou J, Li D, Liu M - PLoS ONE (2014)

HDAC6 regulates LPS-induced M1 response.(A) RAW 264.7 cells pretreated with tubacin were stimulated with LPS (300 ng/ml) for 24 hours. The culture medium was then collected, and the concentrations of IL-6, TNF-α, and IL-10 were measured. (B) Primary BMMs pretreated with tubacin were stimulated with LPS (300 ng/ml) for 24 hours. The culture medium was then collected, and the concentrations of IL-6, TNF-α, and IL-10 were measured. ***, p<0.001; **, p<0.01; ns, not significant (p≥0.05).
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Related In: Results  -  Collection

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pone-0110718-g002: HDAC6 regulates LPS-induced M1 response.(A) RAW 264.7 cells pretreated with tubacin were stimulated with LPS (300 ng/ml) for 24 hours. The culture medium was then collected, and the concentrations of IL-6, TNF-α, and IL-10 were measured. (B) Primary BMMs pretreated with tubacin were stimulated with LPS (300 ng/ml) for 24 hours. The culture medium was then collected, and the concentrations of IL-6, TNF-α, and IL-10 were measured. ***, p<0.001; **, p<0.01; ns, not significant (p≥0.05).
Mentions: Next we investigated the role of HDAC6 in LPS-induced M1 response. RAW264.7 cells and primary BMMs pretreated with tubacin were stimulated with LPS for 24 hours. The pro-inflammatory cytokines IL-6 and TNF-α (M1 markers) and the anti-inflammatory cytokine IL-10 (M2 marker) were then assessed. We found that LPS-induced secretion of IL-6 and TNF-α was dramatically decreased by tubacin in both RAW264.7 cells and primary BMMs; by contrast, LPS-induced IL-10 production was not obviously affected by tubacin (Fig. 2A and 2B). These results suggest that HDAC6 is critical for LPS-induced M1 response.

Bottom Line: However, the molecular mechanisms of how macrophages are activated are not fully understood.Our data show that suppression of HDAC6 activity significantly restrains LPS-induced activation of macrophages and production of pro-inflammatory cytokines.Further study reveals that the regulation of macrophage activation by HDAC6 is independent of F-actin polymerization and filopodium formation; instead, it is mediated by the effects of HDAC6 on cell adhesion and microtubule acetylation.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.

ABSTRACT
Activated macrophages play an important role in both innate and adaptive immune responses, and aberrant activation of macrophages often leads to inflammatory and immune disorders. However, the molecular mechanisms of how macrophages are activated are not fully understood. In this study, we identify a novel role for histone deacetylse 6 (HDAC6) in lipopolysaccharide (LPS)-induced macrophage activation. Our data show that suppression of HDAC6 activity significantly restrains LPS-induced activation of macrophages and production of pro-inflammatory cytokines. Further study reveals that the regulation of macrophage activation by HDAC6 is independent of F-actin polymerization and filopodium formation; instead, it is mediated by the effects of HDAC6 on cell adhesion and microtubule acetylation. These data thus suggest that HDAC6 is an important regulator of LPS-induced macrophage activation and might be a potential target for the management of inflammatory disorders.

Show MeSH
Related in: MedlinePlus