Cytochalasin B Modulates Macrophage-Mediated Inflammatory Responses.
- Author:
Mi Yeon KIM
1
;
Jong Hoon KIM
;
Jae Youl CHO
Author Information
1. Department of Bioinformatics and Life Science, Soongsil University, Seoul 156-743, Republic of Korea.
- Publication Type:Original Article
- Keywords:
Actin cytoskeleton;
Inflammation;
Cytochalasin B;
Macrophages;
TLR4
- MeSH:
Actin Cytoskeleton;
Actins;
Cell Survival;
Cytochalasin B*;
Fluorescein;
Glycoproteins;
HSP27 Heat-Shock Proteins;
Inflammation;
Macrophages;
Membrane Glycoproteins;
Nitric Oxide;
Phosphorylation;
Prostaglandin-Endoperoxide Synthases;
RNA, Messenger;
Toll-Like Receptors;
Tumor Necrosis Factor-alpha
- From:Biomolecules & Therapeutics
2014;22(4):295-300
- CountryRepublic of Korea
- Language:English
-
Abstract:
The actin cytoskeleton plays an important role in macrophage-mediated inflammatory responses by modulating the activation of Src and subsequently inducing nuclear factor (NF)-kappaB translocation. In spite of its critical functions, few papers have examined how the actin cytoskeleton can be regulated by the activation of toll-like receptor (TLR). Therefore, in this study, we further characterized the biological value of the actin cytoskeleton in the functional activation of macrophages using an actin cytoskeleton disruptor, cytochalasin B (Cyto B), and explored the actin cytoskeleton's involvement in morphological changes, cellular attachment, and signaling events. Cyto B strongly suppressed the TLR4-mediated mRNA expression of inflammatory genes such as cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-alpha, and inducible nitric oxide (iNOS), without altering cell viability. This compound also strongly suppressed the morphological changes induced by lipopolysaccharide (LPS), a TLR4 ligand. Cyto B also remarkably suppressed NO production under non-adherent conditions but not in an adherent environment. Cyto B did not block the co-localization between surface glycoprotein myeloid differentiation protein-2 (MD2), a LPS signaling glycoprotein, and the actin cytoskeleton under LPS conditions. Interestingly, Cyto B and PP2, a Src inhibitor, enhanced the phagocytic uptake of fluorescein isothiocyanate (FITC)-dextran. Finally, it was found that Cyto B blocked the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) at 1 min and the phosphorylation of heat shock protein 27 (HSP27) at 5 min. Therefore, our data suggest that the actin cytoskeleton may be one of the key components involved in the control of TLR4-mediated inflammatory responses in macrophages.
