Prenylated quinolinecarboxylic acid compound-18 prevents sensory nerve fiber outgrowth through inhibition of the interleukin-31 pathway
| العنوان: | Prenylated quinolinecarboxylic acid compound-18 prevents sensory nerve fiber outgrowth through inhibition of the interleukin-31 pathway |
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| المؤلفون: | Masato Ogura, Kumiko Endo, Toshiyuki Suzuki, Yoshimi Homma |
| المصدر: | PLoS ONE PLoS ONE, Vol 16, Iss 2, p e0246630 (2021) |
| بيانات النشر: | Public Library of Science, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Cancer Treatment, Carboxylic Acids, Social Sciences, Biochemistry, Ointments, Mice, Nerve Fibers, Dorsal root ganglion, Animal Cells, Ganglia, Spinal, Medicine and Health Sciences, Psychology, Post-Translational Modification, Phosphorylation, STAT3, Topical Medications, Skin, Neurons, Multidisciplinary, Janus kinase 2, biology, Kinase, Chemistry, Applied Mathematics, Cutaneous nerve, Drugs, Cell Differentiation, Cell biology, Precipitation Techniques, medicine.anatomical_structure, Oncology, Quinolines, Medicine, Sensory Perception, Cellular Types, Sensory nerve, Research Article, Signal Transduction, STAT3 Transcription Factor, Neurite, Sensory Receptor Cells, General Mathematics, Science, Immunology, Protein Prenylation, Research and Analysis Methods, Dermatitis, Atopic, Antibody Therapy, Peripheral Nervous System, medicine, Neurites, Immunoprecipitation, Animals, Nerve Growth Factors, Pharmacology, Pruritus, Interleukins, Cognitive Psychology, Biology and Life Sciences, Proteins, Cell Biology, Neuronal Dendrites, Janus Kinase 2, Mice, Inbred C57BL, p21-Activated Kinases, Cellular Neuroscience, biology.protein, STAT protein, Protein prenylation, Cognitive Science, Perception, Clinical Immunology, Clinical Medicine, Neuroscience |
| الوصف: | Interleukin-31 (IL-31) is involved in excessive development of cutaneous sensory nerves in atopic dermatitis (AD), leading to severe pruritus. We previously reported that PQA-18, a prenylated quinolinecarboxylic acid (PQA) derivative, is an immunosuppressant with inhibition of p21-activated kinase 2 (PAK2) and improves skin lesions in Nc/Nga mice as an AD model. In the present study, we investigate the effect of PQA-18 on sensory nerves in lesional skin. PQA-18 alleviates cutaneous nerve fiber density in the skin of Nc/Nga mice. PQA-18 also inhibits IL-31-induced sensory nerve fiber outgrowth in dorsal root ganglion cultures. Signaling analysis reveals that PQA-18 suppresses phosphorylation of PAK2, Janus kinase 2, and signal transducer and activator of transcription 3 (STAT3), activated by IL-31 receptor (IL-31R), resulting in inhibition of neurite outgrowth in Neuro2A cells. Gene silencing analysis for PAK2 confirms the requirement for STAT3 phosphorylation and neurite outgrowth elicited by IL-31R activation. LC/MS/MS analysis reveals that PQA-18 prevents the formation of PAK2 activation complexes induced by IL-31R activation. These results suggest that PQA-18 inhibits the IL-31 pathway through suppressing PAK2 activity, which suppresses sensory nerve outgrowth. PQA-18 may be a valuable lead for the development of a novel drug for pruritus of AD. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::add3c38cb73a9487a001e54fba228248Test http://europepmc.org/articles/PMC7861556Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....add3c38cb73a9487a001e54fba228248 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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