Apolipoprotein J (clusterin) is a component of high-density lipoproteins, the high level of which is reversely correlated with the risk of coronary heart disease. In addition, it exerts anti-inflammatory and anti-apoptotic effects on endothelial cells and inhibits smooth muscle cell migration and proliferation, indicating that it may play a protective role in cardiovascular disease. However, the exact mechanisms by which this occurs remain unclear. This study aimed to clarify these underlying protective mechanisms by researching the inhibitory effects of apolipoprotein J via the NOD-like receptor protein 3 pathway on the inflammation induced by cholesterol crystals in THP‐1 macrophages. In culture, THP-1 macrophages were infected with adenoviral vectors containing apolipoprotein J genes and subsequently treated with cholesterol crystals. The inflammatory cytokines interleukin‐1β, interleukin 18 and tumour necrosis factor α were quantitatively measured with ELISA kits. NOD-like receptor protein 3, cysteinyl aspartate specific proteinase 1 and interleukin 1β were evaluated by Western blot and PCR analysis. As a result, apolipoprotein J expression was found to remarkably decrease the levels of inflammatory cytokines, including tumour necrosis factor α, interleukin 18 and interleukin 1β, secreted by THP‐1 macrophages. It was also found capable of inhibiting the levels of NOD-like receptor protein 3, cysteinyl aspartate-specific proteinase 1 and interleukin 1β both at the protein and mRNA levels. In the current study, we revealed that over-expression of apolipoprotein J attenuated the inflammation induced by cholesterol crystals through inhibition of the NOD-like receptor protein 3 inflammasome pathway.

• MeSH
• cholesterol metabolismus   MeSH
• cytokiny metabolismus   MeSH
• endoteliální buňky metabolismus   patologie   MeSH
• inflamasomy * metabolismus   farmakologie   MeSH
• interleukin-18 metabolismus   MeSH
• interleukin-1beta metabolismus   MeSH
• klusterin metabolismus   farmakologie   MeSH
• kyselina aspartová metabolismus   farmakologie   MeSH
• lidé MeSH
• makrofágy metabolismus   MeSH
• proteasy metabolismus   farmakologie   MeSH
• protein NLRP3 * metabolismus   MeSH
• TNF-alfa metabolismus   MeSH
• zánět patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Monoaminergic neurotransmitter 5-hydroxytryptamine (5-HT), also known as serotonin, plays important roles in modulating the function of the olfactory system. However, thus far, the knowledge about 5-HT and its receptors in olfactory receptor neurons (ORNs) and their physiological role have not been fully characterized. In the present study, reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed the presence of 5-HT(1A) and 5-HT(1B) receptor subtypes in mouse olfactory epithelium at the mRNA level. With subtype selective antibodies and standard immunohistochemical techniques, both receptor subtypes were found to be positively labeled. To further elucidate the molecular mechanisms of 5-HT act on the peripheral olfactory transduction, the whole-cell patch clamp techniques were used on freshly isolated ORNs. We found that 5-HT decreased the magnitude of outward K(+) current in a dose-dependent manner and these inhibitory effects were markedly attenuated by the 5-HT(1A) receptor blocker WAY-100635 and the 5-HT(1B) receptor antagonist GR55562. These data suggested that 5-HT may play a role in the modulation of peripheral olfactory signals by regulating outward potassium currents, both 5-HT(1A) and 5-HT(1B) receptors were involved in this regulation.

• MeSH
• čichové buňky účinky léků   metabolismus   MeSH
• draslíkové kanály účinky léků   metabolismus   MeSH
• membránové potenciály MeSH
• messenger RNA metabolismus   MeSH
• myši MeSH
• receptor serotoninový 5-HT1A účinky léků   genetika   metabolismus   MeSH
• receptor serotoninový 5-HT1B účinky léků   genetika   metabolismus   MeSH
• serotonin metabolismus   MeSH
• serotoninové receptory 5-HT1 - antagonisté farmakologie   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• adenosintrifosfát chemie   MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• Escherichia coli metabolismus   MeSH
• financování organizované MeSH
• fungální proteiny metabolismus   MeSH
• hmotnostní spektrometrie MeSH
• hydrolýza MeSH
• lidé MeSH
• peptidy chemie   MeSH
• proteinfosfatasy chemie   MeSH
• proteiny chemie   MeSH
• sekvence aminokyselin MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• vazebná místa MeSH
• výpočetní biologie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH