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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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Related in: MedlinePlus

Suppression of HDAC6 activity compromises macrophage adhesion to the extracellular matrix, and this effect is abolished in LPS-stimulated macrophages.(A) RAW264.7 cells labeled with calcein-AM were treated with tubacin and seeded in 96-well plates pre-coated with fibronectin or BSA. Cells were washed twice with PBS, and the fluorescence images of cells were captured by a fluorescence microscope before and after wash. (B) Experiments were performed as in panel A, and the fluorescent intensity was measured. The percentage of adherent cells were quantified by dividing the intensity of post-wash with that of pre-wash. (C, D) Experiments and quantifications were performed as in A and B, except that cells were treated with LPS following tubacin treatment. *, p<0.05; ns, not significant (p≥0.05).
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pone-0110718-g004: Suppression of HDAC6 activity compromises macrophage adhesion to the extracellular matrix, and this effect is abolished in LPS-stimulated macrophages.(A) RAW264.7 cells labeled with calcein-AM were treated with tubacin and seeded in 96-well plates pre-coated with fibronectin or BSA. Cells were washed twice with PBS, and the fluorescence images of cells were captured by a fluorescence microscope before and after wash. (B) Experiments were performed as in panel A, and the fluorescent intensity was measured. The percentage of adherent cells were quantified by dividing the intensity of post-wash with that of pre-wash. (C, D) Experiments and quantifications were performed as in A and B, except that cells were treated with LPS following tubacin treatment. *, p<0.05; ns, not significant (p≥0.05).

Mentions: Activated macrophages infiltrate into the affected sites to remove the pathogens. To investigate how HDAC6 exerts its function in macrophage activation, we examined cell adhesion, one of the most important steps during macrophage infiltration. Cells were seeded onto 96-well plates pre-coated with fibronectin or BSA. As shown in Fig. 4A and 4B, inhibition of HDAC6 with tubacin significantly decreased macrophage adhesion to fibronectin. Furthermore, the effect of HDAC6 on cell adhesion was abolished by LPS stimulation (Fig. 4C and 4D). These data suggest that HDAC6 influences macrophage adhesion to the extracellular matrix in resting macrophages, but not in LPS-activated macrophages.


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)

Suppression of HDAC6 activity compromises macrophage adhesion to the extracellular matrix, and this effect is abolished in LPS-stimulated macrophages.(A) RAW264.7 cells labeled with calcein-AM were treated with tubacin and seeded in 96-well plates pre-coated with fibronectin or BSA. Cells were washed twice with PBS, and the fluorescence images of cells were captured by a fluorescence microscope before and after wash. (B) Experiments were performed as in panel A, and the fluorescent intensity was measured. The percentage of adherent cells were quantified by dividing the intensity of post-wash with that of pre-wash. (C, D) Experiments and quantifications were performed as in A and B, except that cells were treated with LPS following tubacin treatment. *, p<0.05; ns, not significant (p≥0.05).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4199742&req=5

pone-0110718-g004: Suppression of HDAC6 activity compromises macrophage adhesion to the extracellular matrix, and this effect is abolished in LPS-stimulated macrophages.(A) RAW264.7 cells labeled with calcein-AM were treated with tubacin and seeded in 96-well plates pre-coated with fibronectin or BSA. Cells were washed twice with PBS, and the fluorescence images of cells were captured by a fluorescence microscope before and after wash. (B) Experiments were performed as in panel A, and the fluorescent intensity was measured. The percentage of adherent cells were quantified by dividing the intensity of post-wash with that of pre-wash. (C, D) Experiments and quantifications were performed as in A and B, except that cells were treated with LPS following tubacin treatment. *, p<0.05; ns, not significant (p≥0.05).
Mentions: Activated macrophages infiltrate into the affected sites to remove the pathogens. To investigate how HDAC6 exerts its function in macrophage activation, we examined cell adhesion, one of the most important steps during macrophage infiltration. Cells were seeded onto 96-well plates pre-coated with fibronectin or BSA. As shown in Fig. 4A and 4B, inhibition of HDAC6 with tubacin significantly decreased macrophage adhesion to fibronectin. Furthermore, the effect of HDAC6 on cell adhesion was abolished by LPS stimulation (Fig. 4C and 4D). These data suggest that HDAC6 influences macrophage adhesion to the extracellular matrix in resting macrophages, but not in LPS-activated macrophages.

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