{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T23:53:20Z","timestamp":1785196400377,"version":"3.55.0"},"reference-count":29,"publisher":"Asian Spine Journal (ASJ)","issue":"6","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K16697"],"award-info":[{"award-number":["17K16697"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K18506"],"award-info":[{"award-number":["19K18506"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asianspinejournal.org"],"crossmark-restriction":true},"short-container-title":["Asian Spine J"],"published-print":{"date-parts":[[2023,12,31]]},"abstract":"<jats:p>Study Design: This experimental study was performed using human ligamentum flavum\u2013derived cells (HFCs).Purpose: To investigate the intracellular signaling mechanism of interleukin-6 (IL-6) secretion in transforming growth factor-\u03b2 (TGF- \u03b2)-stimulated HFCs.Overview of Literature: Lumbar spinal stenosis (LSS) is a prevalent disease among the elderly, characterized by debilitating pain in the lower extremities. Although the number of patients with LSS has increased in recent years, the underlying pathomechanism remains unclear. Clinical examinations typically rely on magnetic resonance imaging to diagnose patients, revealing ligamentum flavum hypertrophy. Some studies have suggested an association between ligamentum flavum hypertrophy and inflammation\/fibrosis, and expression of TGF-\u03b2 and IL-6 has been observed in surgically obtained ligamentum flavum samples. However, direct evidence linking TGF-\u03b2 and IL-6 expression in HFCs is lacking.Methods: HFCs were obtained from patients with LSS who had undergone decompression surgery. The cells were stimulated with TGF-\u03b2 and pretreated with either the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 or the p44\/42 MAP kinase inhibitor FR180204. IL-6 secretion in the cell culture medium and IL-6 messenger RNA (mRNA) expression levels were analyzed using an enzyme-linked immunoassay and real-time polymerase chain reaction, respectively.Results: TGF-\u03b2 administration resulted in a dose- and time-dependent stimulation of IL-6 release. Treatment with SB203580 and FR180204 markedly suppressed TGF-\u03b2\u2013induced IL-6 secretion from HFCs. Moreover, these inhibitors suppressed IL-6 mRNA expression in response to TGF-\u03b2 stimulation.Conclusions: Our findings indicate that TGF-\u03b2 induces IL-6 protein secretion and gene expression in HFCs through the activation of p38 or p44\/42 MAP kinases. These results suggest a potential association between IL-6\u2013mediated inflammatory response and tissue hypertrophy in LSS, and we provide insights into molecular targets for therapeutic interventions targeting LSS-related inflammation through our analysis of the MAP kinase pathway using HFCs.<\/jats:p>","DOI":"10.31616\/asj.2023.0025","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T05:15:51Z","timestamp":1699593351000},"page":"997-1003","update-policy":"https:\/\/doi.org\/10.31616\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Transforming Growth Factor-\u03b2 Induces Interleukin-6 Secretion from Human Ligamentum Flavum\u2013Derived Cells through Partial Activation of p38 and p44\/42 Mitogen-Activated Protein 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