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Human THP\u20101 macrophages (THP\u20101m), differentiated from THP\u20101 cells by phorbol 12\u2010myristate 13\u2010acetate, were used to investigate the immune function of hMIKO\u20101 as a drug for inflammatory diseases. Western blotting was conducted to confirm whether hMIKO\u20101 binds with \u03b2\u2010actin and nuclear factor\u2010kappa B to form complexes in THP\u20101m. A polymerase chain reaction (PCR) and quantitative PCR were performed to examine changes in the messenger RNA levels of proinflammatory cytokines in THP\u20101m. Fluorescent immunochemical staining was used to observe the intracellular localization of hMIKO\u20101 and hS100A8 or hS100A9 in THP\u20101m. As observed microscopically, the intracellular localization of hMIKO\u20101 in THP\u20101m was consistent with that of hS100A8, suggesting the close involvement of hS100A8 in the intracellular behavior of hMIKO\u20101 in THP\u20101m. Western blotting revealed that hMIKO\u20101 formed complexes with intracellular proteins, such as \u03b2\u2010actin and nuclear factor\u2010kappa B, to negatively regulate inflammatory signal transduction in THP\u20101m. Flow cytometry showed that the binding of hMIKO\u20101 to THP\u20101m significantly decreased when THP\u20101m were preliminarily treated with a sialidase (neuraminidases) cocktail. Therefore, the present results strongly suggest that the binding of hMIKO\u20101 to THP\u20101m closely involves the sugar chains of the surface proteins of cells. The messenger RNA expression of each proinflammatory cytokine was significantly suppressed in THP\u20101m preliminarily treated with hMIKO\u20101 despite a subsequent stimulation with lipopolysaccharide. In conclusion, hMIKO\u20101 is a functional molecule that significantly inhibits inflammatory signal transduction in THP\u20101m.<\/jats:p>","DOI":"10.1111\/imcb.70000","type":"journal-article","created":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T11:49:41Z","timestamp":1739620181000},"page":"350-364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A hybrid protein is a functional molecule to reduce the cytokine storm caused by excessively activated macrophages"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6712-3660","authenticated-orcid":false,"given":"Masaki","family":"Ikemoto","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine IV Osaka Medical and Pharmaceutical University  Osaka 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