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The role of Rho-kinases in IL-1β release through phagocytosis of fibrous particles in human monocytes

  • Molecular Toxicology
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Abstract

Long fibers, such as asbestos and carbon nanotubes (CNTs), are more potent activators of inflammatory and genotoxicity than short or tangled fibers. Fibrous particles trigger interleukin (IL)-1β secretion and cause inflammatory diseases through NLRP3 inflammasomes in phagocytotic cells. However, the mechanism involved in fibrous particle-induced inflammation has not been well documented. In this study, we focused on GTPase effector Rho-kinases (ROCK1, and 2), which are known to be involved in a wide range of cellular functions such as adhesion, regulation of cytoskeleton, and phagocytosis. We examined whether ROCKs are associated with multi-walled CNT (MWCNT)- or asbestos-induced IL-1β secretion in human monocytic THP-1 cells using a selective inhibitor and small interfering RNA. THP-1 cells were differentiated to macrophages by PMA and were exposed to MWCNTs, crocidolite asbestos or lipopolysaccharide (LPS) in the presence or absence of Y27632 (ROCK inhibitor) or Z-YVAD (caspase-1 inhibitor). Exposure of the cells to MWCNTs or asbestos provoked IL-1β secretion, but this secretion was suppressed by both Y27632 and Z-YVAD, whereas LPS-induced IL-1β secretion was inhibited only by Z-YVAD and not by Y27632. siRNA designed for knockdown of both ROCK1 and ROCK2 suppressed MWCNT- and asbestos-induced IL-1β secretion, but did not change LPS-induced IL-1β secretion. Moreover, Y27632 suppressed pro-IL-1β protein levels and the release of activated-cathepsin B and activated-caspase-1 induced by MWCNTs or asbestos. In contrast, LPS-induced pro-IL-1β protein was not suppressed by Y27632. These results suggest that ROCKs are involved in fibrous particle-induced inflammasome responses in THP-1 cells.

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Acknowledgments

We would like to thank Mr. T. Ikawa for the technical support. This work was supported by JSPS KAKENHI (Grant No. 24590868).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan

    Sanae Kanno, Shoetsu Chiba, Hiroshi Takeshita, Tomonori Nagai, Meri Takada, Kana Sakamoto & Toshiji Mukai

  2. Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, 305-8506, Japan

    Seishiro Hirano

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  1. Sanae Kanno
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  2. Seishiro Hirano
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Correspondence to Sanae Kanno.

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Kanno, S., Hirano, S., Chiba, S. et al. The role of Rho-kinases in IL-1β release through phagocytosis of fibrous particles in human monocytes. Arch Toxicol 89, 73–85 (2015). https://doi.org/10.1007/s00204-014-1238-2

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