| First Author | Kim TH | Year | 2021 |
| Journal | Cell Death Dis | Volume | 12 |
| Issue | 1 | Pages | 19 |
| PubMed ID | 33414479 | Mgi Jnum | J:336618 |
| Mgi Id | MGI:6802937 | Doi | 10.1038/s41419-020-03332-w |
| Citation | Kim TH, et al. (2021) Apoptosis inhibitor of macrophage (AIM) contributes to IL-10-induced anti-inflammatory response through inhibition of inflammasome activation. Cell Death Dis 12(1):19 |
| abstractText | Apoptosis inhibitor of macrophage (AIM) modulates the signaling in inflammatory responses, including infection, cancer, or other immune diseases. Recent studies suggest that like interleukin-10 (IL-10), AIM is involved in alternatively activated (M2) macrophage polarization. We aimed to understand whether and how AIM is involved in IL-10-induced inhibition of inflammasome activation and resolution of inflammation. First, we demonstrated that IL-10 induced increases in mRNA and protein expression of AIM in murine bone marrow-derived macrophages (BMDM). In addition, genetic and pharmacologic inhibition of STAT3 (signal transducer and activator of transcription 3) reduced IL-10-induced AIM expression. We also found that IL-10-induced STAT3 activity enhanced the AIM promoter activity by directly binding the promoter of the AIM gene. Additionally, reduction of LPS/adenosine triphosphate (ATP)-induced IL-1beta production and caspase-1 activation by IL-10 was reversed in BMDM from AIM(-/-) mice. Treatment of BMDM from both wild type (WT) and IL-10(-/-) mice with recombinant AIM showed the inhibitory effects on IL-1beta and IL-18 production and caspase-1 activation. Endogenous and exogenous AIM inhibited apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) speck formation. In LPS-induced acute peritonitis, inhibition of IL-1beta and IL-18 production in peritoneal lavage fluid (PLF) and serum, reduction of caspase-1 activation in peritoneal macrophages, and reduction of numbers of neutrophils and peritoneal macrophages in PLF by administration of IL-10 were not evident in AIM(-/-) mice. Our in vitro and in vivo data reveal a novel role of AIM in the inhibition of inflammasome-mediated caspase-1 activation and IL-1beta and IL-18 production. |
