The investigation of immunomodulatory effects of didemnin B in macrophage cells


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Dag H. E., Atalay B. R., Ayaz F., Ayaz E. A., Deviren A.

IMMUNOLOGIC RESEARCH, cilt.74, sa.1, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 74 Sayı: 1
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1007/s12026-026-09761-7
  • Dergi Adı: IMMUNOLOGIC RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Hayır

Özet

Didemnins, which are cyclic depsipeptides originating from marine sources, have gained significant interest owing to their potent anti-cancer properties. Among them, Didemnin B exhibits potent anti-tumor effects; however, its poor bioavailability and dose-limiting toxicity have thus far restricted its clinical application. Understanding its immunological impact is therefore essential for optimizing its therapeutic potential and supporting ongoing efforts to develop Didemnin B as a clinically viable agent. This study aimed to investigate the immunomodulatory effects of Didemnin B on macrophage function, with a particular focus on its potential relevance to immunotherapeutic and chemotherapeutic applications. In this context, Didemnin B was applied at concentrations of 1, 5, and 10 & micro;g/mL to RAW 264.7 macrophages, based on dose ranges previously reported in the literature. The production of TNF-alpha, IL-6, GM-CSF, and IL-12p40 was evaluated under both unstimulated and LPS-stimulated conditions. Cytokine levels in cell culture supernatants were measured using ELISA to assess how Didemnin B modulates macrophage cytokine responses. Our findings demonstrate that Didemnin B suppresses the production of TNF-alpha, IL-6, GM-CSF, and IL-12p40 in RAW 264.7 macrophages, indicating a robust inhibitory effect on pro-inflammatory cytokine secretion. Didemnin B significantly attenuates LPS-induced inflammatory responses in RAW 264.7 macrophages by suppressing key pro-inflammatory cytokines, indicating its potential as a potent anti-inflammatory and immunomodulatory agent.