open access

https://hdl.handle.net/2115/82819

Gasdermin D-independent release of interleukin‐1β by living macrophages in response to mycoplasmal lipoproteins and lipopeptides

英語

plasma membrane permeabilization

2020-10

John Wiley & Sons

Immunology

161(2)

114-122

Interleukin-1 beta (IL-1 beta) plays pivotal roles in controlling bacterial infections and is produced after the processing of pro-IL-1 beta by caspase-1, which is activated by the inflammasome. In addition, caspase-1 cleaves the cytosolic protein, gasdermin-D (GSDMD), whose N-terminal fragment subsequently forms a pore in the plasma membrane, leading to the pyroptic cell-death-mediated release of IL-1 beta. Living cells can also release IL-1 beta via GSDMD pores or other unconventional secretory pathways. However, the precise mechanisms are poorly defined. Here, we show that lipoproteins fromMycoplasma salivarium (MsLP) andMycoplasma pneumoniae (MpLP) and an M. salivarium-derived lipopeptide (FSL-1), which are activators of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, induce IL-1 beta release from mouse bone-marrow-derived macrophages (BMMs) without inducing cell death. The levels of IL-1 beta release induced by MsLP, MpLP and FSL-1 were more than 100 times lower than those induced by the canonical NLRP3 activator nigericin. The IL-1 beta release-inducing activities of MsLP, MpLP and FSL-1 were not attenuated in BMMs from GSDMD-deficient mice. Furthermore, both active caspase-1 and cleaved GSDMD were detected in response to transfection of FSL-1 into the cytosol of BMMs, but the release of IL-1 beta was unaffected by GSDMD deficiency. Meanwhile, punicalagin, a membrane-stabilizing agent, drastically down-regulated the release of IL-1 beta in response to FSL-1. These results suggest that mycoplasmal lipoprotein/lipopeptide-induced IL-1 beta release by living macrophages is not mediated via GSDMD but rather through changes in membrane permeability.

学術雑誌論文

Accepted Manuscript

This is the peer reviewed version of the following article: [Saeki A, Tsuchiya K, Suda T, Into T, Hasebe A, Suzuki T, Shibata KI. Gasdermin D-independent release of interleukin-1β by living macrophages in response to mycoplasmal lipoproteins and lipopeptides. Immunology. 2020 Jun 26;161(2):114–22.], which has been published in final form at [https://doi.org/10.1111/imm.13230]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."

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