Mycophenolic Acid Synergizing with Lipopolysaccharide to Induce Interleukin-1β Release via Activation of Caspase-1 / 中华医学杂志(英文版)

<p><b>Background</b>The previous study showed that mycophenolic acid (MPA) synergizing with lipopolysaccharide (LPS) promoted interleukin (IL)-1β release, but the mechanism is unclear. This study aimed to investigate the mechanism of MPA synergizing with LPS to induce IL-1β release.</p><p><b>Methods</b>Undiluted human blood cells, THP-1 human myeloid leukemia mononuclear cells (THP-1) cells, or monocytes were stimulated with LPS and treated with or without MPA, and the supernatant IL-1β was detected by enzyme-linked immunosorbent assay. The mRNA levels of IL-1β were detected by real-time quantitative polymerase chain reaction. The intracellular protein levels of nuclear factor kappa B (NF-κB) phospho-p65 (p-p65), precursor interleukin-1β (pro-IL-1β), NOD-like receptor pyrin domain containing-3 (NLRP3), and cysteine aspartic acid-specific protease-1 (caspase-1) p20 in THP-1 cell were measured by Western blot.</p><p><b>Results</b>The MPA alone failed to induce IL-1β, whereas MPA synergized with LPS to increase IL-1β in a dose-dependent manner (685.00 ± 20.00 pg/ml in LPS + 5 μmol/L MPA group, P = 0.035; 742.00 ± 31.58 pg/ml in LPS + 25 μmol/L MPA group, P = 0.017; 1000.00 ± 65.59 pg/ml in LPS + 75 μmol/L MPA group, P = 0.024; versus 408.00 ± 35.50 pg/ml in LPS group). MPA alone has no effect on the IL-1β mRNA expression, LPS induced the expression of IL-1β mRNA 2761 fold, and LPS + MPA increased the IL-1β expression 3018 fold, which had the same effect with LPS group (P = 0.834). MPA did not affect the intracellular NF-κB p-p65 and pro-IL-1β protein levels but activated NLRP3 inflammasome. Ac-YVAD-cmk blocked the activation of caspase-1 and subsequently attenuated IL-1β secretion (181.00 ± 45.24 pg/ml in LPS + MPA + YVAD group vs. 588.00 ± 41.99 pg/ml in LPS + MPA group, P = 0.014).</p><p><b>Conclusions</b>Taken together, MPA synergized with LPS to induce IL-1β release via the activation of caspase-1, rather than the enhanced production of pro-IL-1β. These findings suggested that patients immunosuppressed with mycophenolate mofetil may have overly activated caspase-1 during infection, which might contribute to a more sensitive host defense response to invading germs.</p>

Hydrogen sulfide alleviates chlorobenzene toxicity in soybean seedlings / Sulfeto de hidrogênio e clorobenzeno na toxicidade da soja

ABSTRACT: As a gas signaling molecule, endogenous hydrogen sulfide (H2S) plays a crucial role in the plant stress response. However, the role of H2S in the response to organic pollutants specifically has not been studied. Here, the effects of H2S addition on soybean (Glycine max) seedlings tolerance of 1,4-dichlorobenzene (1,4-DCB) were investigated. Under 1,4-DCB stress, the growth of soybean seedlings roots and stems was inhibited, while L-/D-cysteine desulfhydrase (LCD/DCD) activity was induced and endogenous H2S increased. When applied jointly with sodium hydrosulfide (NaHS), a H2S donor, root growth inhibition was effectively alleviated. Pre-treatment of seedlings with 0.4mmol L-1 NaHS reduced the malondialdehyde (MDA) and reactived oxygen species (ROS) content, mitigating root cell toxicity significantly. Further experiments confirmed that NaHS enhanced soybean seedlings peroxidase (POD) and superoxide dismutase (SOD) enzyme activities. In contrast, these effects were reversed by hypotaurine (HT), a H2S scavenger. Therefore, H2S alleviated 1,4-DCB toxicity in soybean seedlings by regulating antioxidant enzyme activity to reduce cell oxidative damage.

RESUMO: Tal como uma molécula de sinal de gás, sulfureto de hidrogenio endógena (H2S) desempenha um papel crucial na resposta ao stress das plantas. Mas não foi relatado o papel de H2S em plantas poluentes orgânicos stress. Este estudo sobre a variação de H2S envolvido em plântulas de soja tolerância 1,4-Diclorobenzeno foi investigada. Os resultados mostraram sob o 1,4-diclorobenzeno stress, que o crescimento da soja (Glycine max) de raiz de mudas e caule foram inibidas, L- / D-cisteína desulfhydrase (LCD / DCD) atividades enzimáticas foram empossados, em seguida, H2S endógeno aumentado. Quando aplicado com hidrossulfureto de sódio (NaSH), um doador de H2S, raiz de plântulas de soja, a inibição do crescimento pode ser melhorada. Tratamentos prévios com 0,4mmol L-1 NaHS, malondialdeído (MDA) e espécies de oxigênio reactivas conteúdo (ROS) foi reduzida, em seguida, a toxicidade celular da raiz foi reduzida significativamente. Outros experimentos confirmaram que NaSH melhorou a peroxidase de plântulas de soja (POD), superóxido dismutase (SOD) atividades enzimáticas. Em contraste, estes efeitos foram revertidos por hypotaurine (HT), um eliminador de H2S. Então H2S pode aliviar toxicidade 1,4-diclorobenzeno em plântulas de soja por meio da regulamentação das atividades de enzimas antioxidantes para manter a integridade da estrutura celular.