Kosin Medical Journal

Original article

Gangliosides enhance M2-polarized macrophage elongation induced by IL-4 and IL-13: Snehal Chandrakant Meshram, Hee-Jin Choi, Minkyoung Cho, Jaewon Shim, Ki-Tae Ha, Sung-Jin Bae; Kosin Med J. 2025;40(3):188-198. Published online September 18, 2025; DOI: https://doi.org/10.7180/kmj.25.113

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Background
Macrophage polarization plays a crucial role in the immune response, and gangliosides regulate macrophage function. In this study, we investigated the role of gangliosides in modulating macrophage morphology and function in response to M2 polarization induced by interleukin (IL)-4 and IL-13.
Methods
The mouse monocyte/macrophage cell line RAW264.7 and bone marrow macrophages were used to assess the role of gangliosides in macrophages. Additionally, St3gal5 knockdown was achieved using small interfering RNA constructs for further examinations.
Results
Elongation of M2-polarized macrophages in the presence of IL-4 and IL-13 was associated with increased ganglioside synthesis, as shown by reverse transcription-polymerase chain reaction and immunoblot analyses. Pretreatment with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol and St3gal5 knockdown significantly reduced elongation, indicating that gangliosides play a substantial role in this process. Flow cytometry revealed that ganglioside monosialodihexosylganglioside (GM3) and ganglioside disialodihexosylganglioside (GD3) expression was significantly upregulated in M2-polarized macrophages. Moreover, transwell migration assays demonstrated that GM3 promoted macrophage migration, and this effect was abrogated by St3gal5 knockdown. Despite increased elongation and migration, phagocytic activity was reduced in elongated macrophages, as measured by the phagocytosis index using latex beads, which was reversed upon St3gal5 knockdown. Additionally, GM3 treatment activated the protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways, as confirmed by immunoblot analysis, demonstrating their role in ganglioside-induced elongation.
Conclusions
Our findings highlight the crucial role of gangliosides in regulating the morphological plasticity of macrophages via AKT and ERK activation to promote elongation, which results in increased migration and reduced phagocytosis. This study provides insights into the mechanism by which gangliosides influence macrophage function and immune responses.

Citations

Citations to this article as recorded by

Ganglioside-mediated macrophage plasticity
Jeongtae Kim
Kosin Medical Journal.2025; 40(3): 157. CrossRef

Review articles

Exploring the influence of olfactory receptors in metabolic diseases and cancers: beyond sensory functions: In-sun Yu, Jeong Sook Ye, Jaewon Shim; Kosin Med J. 2025;40(1):15-20. Published online February 17, 2025; DOI: https://doi.org/10.7180/kmj.24.142

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Olfactory receptors (ORs), which are primarily responsible for olfactory sensation in the nasal epithelium, constitute the largest family of genes in the human genome. The majority of ORs are orphan receptors with unknown ligands; however, recent studies have revealed their expression in non-olfactory tissues, implying that ORs may be involved in various physiological processes beyond olfaction. This review highlights recent findings on the roles of ORs in cancers, including prostate, breast, and lung cancer, as well as their involvement in other diseases, such as atherosclerosis, Alzheimer's disease, and viral infections. Additionally, we explore emerging knowledge about the role of ORs in metabolic regulation, focusing on their effect on triglyceride metabolism, glucagon-like peptide-1 secretion, and lipid accumulation. Advancements in technology, such as structural analysis, have accelerated research on OR ligands and their functions, potentially positioning ORs as novel therapeutic targets for various diseases. This review highlights the need for further research into the non-olfactory roles of ORs and their potential as targets for future therapeutic interventions.

Citations

Citations to this article as recorded by

Decoding the Molecular Mechanisms of Menthol Isomer Perception Based on Computational Simulations
Mengxue Wang, Fengge Wen, Lili Zhang, Baoguo Sun, Jianping Xie, Shihao Sun, Yuyu Zhang
Foods.2025; 14(14): 2494. CrossRef

Considerations for experimental animal ethics in the research planning and evaluation process: Jaewon Shim, Jeongtae Kim; Kosin Med J. 2022;37(4):271-277. Published online December 22, 2022; DOI: https://doi.org/10.7180/kmj.22.139

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Research using experimental animals has substantially contributed to advances in science and medicine. Animal experiments are nearly essential for biomedical research and development efforts. Because many animals are sacrificed, researchers should consider the welfare of experimental animals and related ethical issues, along with the successful results of their experiments. This review introduces the criteria that should be considered in terms of experimental animal ethics, based on the principles of the 3 R’s: replacement, representing careful consideration of the need for animal experiments; reduction, representing the use of the minimal number of animals to obtain meaningful experimental results; and refinement, representing continuous effects to find alternative methods to reduce pain and distress in experimental animals. Based on these principles, the following points should be considered when planning experiments: the necessity of animal experiments; alternatives to animal experiments; the relevance of the species and numbers of experimental animals; appropriate assessment and management of pain; the proper usage of sedatives, painkillers, and anesthesia; and valid timing for humane endpoints and euthanasia. These criteria are beneficial for both experimental animals and researchers because careful handling to ensure experimental animal welfare guarantees that scientific research will yield convincing, repeatable, and accurate results.

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