The findings of a previous study by Jin et al. have shown that microRNA (miR)-155 was upregulated in patients with acute gouty arthritis and enhanced the proinflammatory cytokines. There is no direct evidence to support that miR-155 is indeed involved in monosodium urate (MSU)-induced inflammatory responses in vivo. The aim of this study was to investigate the role of miR-155 knock-out (KO) or knock-in (KI) mice in MSU-induced animal models to mimic acute gout. MiR-155 expression in cultured bone marrow-derived macrophages (BMDMs) from miR-155 KO, miR-155 KI, and wild-type (WT) mice treated with MSU crystals in vitro was detected by real-time quantitative polymerase chain reaction (qPCR). MiR-155 KO and WT mice were used to induce an acute gouty inflammatory response with MSU crystals including models of foot pad inflammation, ankle arthritis, air pouch inflammation, and peritonitis. Furthermore, the proinflammatory interleukin (IL)-1β levels in lavage fluids from air pouch and peritoneal cavity models were measured by enzyme-linked immunosorbent assay (ELISA), and tumor necrosis factor (TNF)-α production from BMDMs of miR-155 KI mice treated with MSU were measured by flow cytometry. MiR-155 expression was quickly upregulated in BMDMs from WT mice following MSU treatment in vitro. In comparison with WT mice in vivo, the swelling index of miR-155 KO mice showed no significant difference in the murine foot pad and ankle arthritis models for the indicated different time points. There were similar changes in total cell numbers of lavage fluids in the air pouch and peritoneal cavity models between miR-155 KO and WT mice following MSU crystal injection. Moreover, the IL-1β levels of lavage fluids in the air pouch and peritonitis models from miR-155 KO mice were almost the same as those from WT mice. TNF-α levels were comparable from BMDMs treated with MSU crystals in vitro between miR-155 KI mice and WT mice. MiR-155 is dispensable in MSU-induced gouty inflammation in mice. Deletion of miR-155 might not be an effective therapeutic approach to relieve the inflammation in acute gout.

Gout is sterile joint inflammation triggered by the damaging effects of monosodium urate (MSU) crystals accumulation. Previous studies suggest transcription factor T-bet plays an important role in inflammatory arthritis. Notably, mice lacking T-bet markedly reduced joint inflammation of rheumatoid arthritis models, however, the involvement of T-bet in gouty inflammation has yet to be clarified. Here, we took advantage of T-bet knockout (KO) mice to investigate the role of T-bet in the pathogenesis of MSU-induced gout inflammation. T-bet KO and wild type (WT) mice were used for models of acute inflammation induced with MSU crystals, including footpad, air pouch and peritonitis models. Inflammatory cytokines and phagocytosis were detected in bone-marrow-derived macrophages (BMDMs) from T-bet KO and WT mice treated with MSU crystals in vitro. In addition, T-bet expression in peripheral blood mononuclear cells (PBMCs) from gout patients was measured, as well as plasma inflammatory cytokines. We found that the levels of interleukin (IL)-17, IL-23, and interferon-γ were reduced, but tumor necrosis factor-α was not, in BMDMs from T-bet KO compared with WT mice after MSU challenge in vitro, as well as MSU phagocytosis. In comparison with WT mice in vivo, the swelling index of T-bet KO mice was significantly decreased in the footpad model. T-bet deficiency also dramatically relieved MSU-induced inflammatory cell infiltration in peritonitis and air pouch models in vivo, and as well as the IL-1β levels of air pouch lavage fluid (APLF). In addition, plasma IL-17 and IL-23 levels were elevated in acute gout, whereas protein levels of T-bet were downregulated in PBMCs from acute gout patients and intercritical gout treated with MSU crystals in vitro as well. Transcription factor T-bet deficiency protects against MSU-induced gouty inflammation, suggesting that downregulation of T-bet could be a protective strategy and contribute to spontaneous remission of inflammation in acute gout.

Background: Gout is caused by monosodium urate (MSU) crystals deposition to trigger immune response. A recent study suggested that inhibition of Class I Histone deacetylases (HDACs) can significantly reduce MSU crystals-induced inflammation. However, which one of HDACs members in response to MSU crystals was still unknown. Here, we investigated the roles of HDAC3 in MSU crystals-induced gouty inflammation. Methods: Macrophage specific HDAC3 knockout (KO) mice were used to investigate inflammatory profiles of gout in mouse models in vivo, including ankle arthritis, foot pad arthritis and subcutaneous air pouch model. In the in vitro experiments, bone marrow-derived macrophages (BMDMs) from mice were treated with MSU crystals to assess cytokines, potential target gene and protein. Results: Deficiency of HDAC3 in macrophage not only reduced MSU-induced foot pad and ankle joint swelling but also decreased neutrophils trafficking and IL-1β release in air pouch models. In addition, the levels of inflammatory genes related to TLR2/4/NF-κB/IL-6/STAT3 signaling pathway were significantly decreased in BMDMs from HDAC3 KO mice after MSU treatment. Moreover, RGFP966, selective inhibitor of HDAC3, inhibited IL-6 and TNF-α production in BMDMs treated with MSU crystals. Besides, HDAC3 deficiency shifted gene expression from pro-inflammatory macrophage (M1) to anti-inflammatory macrophage (M2) in BMDMs after MSU challenge. Conclusions: Deficiency of HDAC3 in macrophage alleviates MSU crystals-induced gouty inflammation through inhibition of TLR2/4 driven IL-6/STAT3 signaling pathway, suggesting that HDAC3 could contribute to a potential therapeutic target of gout.

Salinity is a crucial environmental factor influencing the survival, growth, development, and reproduction of aquatic animals. However, the underlying molecular mechanisms of the shrimp’s response to salinity stress are not yet fully understood. Therefore, we used the Illumina NovaSeq 6000 platform to perform transcriptome sequencing of the hepatopancreas of Litopenaeus vannamei under high-salinity (30 PSU), medium-salinity (10 PSU), and low-salinity (0.5 PSU) conditions. We obtained 63.23 Gb of high-quality data and identified 3589 differentially expressed genes (DEGs), including 1638 upregulated and 1951 downregulated genes. Notably, a comparison between the control group (30 PSU) and the low-salinity group (0.5 PSU) revealed that the BBOX1 and CHE1 genes were significantly upregulated, while the ACOX1, MPV, CYP2L1, GCH, MVK, TREt1, and XDH genes were significantly downregulated. These genes are primarily involved in key metabolic pathways, such as fatty acid oxidation, cholesterol metabolism, and hormone synthesis and metabolism. The key genes involved in fatty acid β-oxidation, such as ACOX1, ACAD, HADH, HSD17B4, PECR, CROT, PIPOX, and CG5009, all showed a downward trend, suggesting that L. vannamei may respond to salt stress by regulating fatty acid oxidative metabolism, optimizing energy utilization, and maintaining cell homeostasis under low-salinity conditions. Functional annotation of gene ontology (GO) and KEGG pathway enrichment analysis highlighted the roles of these significant DEGs in the adaptation of L. vannamei to environments of varying salinity, underscoring the importance of metabolic pathways in their adaptive physiological responses. This study provides a crucial molecular biological basis for understanding the molecular mechanisms and physiological protection strategies of L. vannamei under salinity stress.