Nejvíce citovaný článek - PubMed ID 30876862
Biochemistry of very-long-chain and long-chain ceramides in cystic fibrosis and other diseases: The importance of side chain
Coronavirus infections are frequent viral infections in several species. As soon as the severe acute respiratory syndrome (SARS) appeared in the early 2000s, most of the research focused on pulmonary disease. However, disorders in immune response and organ dysfunctions have been documented. Elderly individuals with comorbidities exhibit worse outcomes in all the coronavirus that cause SARS. Disease severity in SARS-CoV-2 infection is related to severe inflammation and tissue injury, and effective immune response against the virus is still under analysis. ACE2 receptor expression and polymorphism, age, gender and immune genetics are factors that also play an essential role in patients' clinical features and immune responses and have been partially discussed. The present report aims to review the physiopathology of SARS-CoV-2 infection and propose new research topics to understand the complex mechanisms of viral infection and viral clearance.
- Klíčová slova
- SARS-CoV-2 infection, complement, coronavirus, cytokine storm, immune response, innate immune response, memory cells,
- MeSH
- angiotensin-konvertující enzym 2 genetika metabolismus MeSH
- biologické markery MeSH
- COVID-19 komplikace imunologie metabolismus virologie MeSH
- cytokiny metabolismus MeSH
- energetický metabolismus MeSH
- interakce hostitele a patogenu imunologie MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- náchylnost k nemoci imunologie MeSH
- podskupiny lymfocytů imunologie metabolismus MeSH
- přirozená imunita MeSH
- receptor angiotensinu typ 2 metabolismus MeSH
- replikace viru MeSH
- SARS-CoV-2 fyziologie MeSH
- syndrom uvolnění cytokinů etiologie metabolismus MeSH
- virové receptory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- ACE2 protein, human MeSH Prohlížeč
- angiotensin-konvertující enzym 2 MeSH
- biologické markery MeSH
- cytokiny MeSH
- mediátory zánětu MeSH
- receptor angiotensinu typ 2 MeSH
- virové receptory MeSH
PURPOSE: To assess the efficacy of the novel clinical formulation of fenretinide (LAU-7b) for the treatment of allergic asthma. To study the association between LAU-7b treatment in allergic asthma and the modulation of very long chain ceramides (VLCC). METHODS: We used two allergens (OVA and HDM) to induce asthma in mouse models and we established a treatment protocol with LAU-7b. The severity of allergic asthma reaction was quantified by measuring the airway resistance, quantifying lung inflammatory cell infiltration (Haematoxylin and eosin stain) and mucus production (Periodic acid Schiff satin). IgE levels were measured by ELISA. Immunophenotyping of T cells was done using Fluorescence-activated cell sorting (FACS) analysis. The analysis of the specific species of lipids and markers of oxidation was performed using mass spectrometry. RESULTS: Our data demonstrate that 10 mg/kg of LAU-7b was able to protect OVA- and HDM-challenged mice against increase in airway hyperresponsiveness, influx of inflammatory cells into the airways, and mucus production without affecting IgE levels. Treatment with LAU-7b significantly increased percentage of regulatory T cells and CD4+ IL-10-producing T cells and significantly decreased percentage of CD4+ IL-4-producing T cells. Our data also demonstrate a strong association between the improvement in the lung physiology and histology parameters and the drug-induced normalization of the aberrant distribution of ceramides in allergic mice. CONCLUSION: 9 days of 10 mg/kg of LAU-7b daily treatment protects the mice against allergen-induced asthma and restores VLCC levels in the lungs and plasma.
- Klíčová slova
- LAU-7b, allergic asthma, fenretinide, very long chain ceramides,
- MeSH
- alergeny imunologie MeSH
- bronchiální astma farmakoterapie imunologie metabolismus MeSH
- ceramidy metabolismus MeSH
- fenretinid terapeutické užití MeSH
- klinické protokoly MeSH
- methylcelulosa chemie MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- ovalbumin imunologie MeSH
- příprava léků MeSH
- Pyroglyphidae imunologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alergeny MeSH
- ceramidy MeSH
- fenretinid MeSH
- methylcelulosa MeSH
- ovalbumin MeSH