Biomol Ther.  2014 Jul;22(4):295-300.

Cytochalasin B Modulates Macrophage-Mediated Inflammatory Responses

• Kim MY
• Kim JH
• Cho JY

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.

Keyword

Actin cytoskeleton; Inflammation; Cytochalasin B; Macrophages; TLR4

MeSH Terms

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
Actins
Cytochalasin B
Fluorescein
Glycoproteins
HSP27 Heat-Shock Proteins
Membrane Glycoproteins
Nitric Oxide
Prostaglandin-Endoperoxide Synthases
RNA, Messenger
Toll-Like Receptors
Tumor Necrosis Factor-alpha