{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:45:57Z","timestamp":1773798357326,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["21K08450"],"award-info":[{"award-number":["21K08450"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although interstitial lung disease (ILD) is a life-threatening pathological condition that causes respiratory failure, the efficiency of current therapies is limited. This study aimed to investigate the effects of human MIKO-1 (hMIKO-1), a hybrid protein that suppresses the abnormal activation of macrophages, on murine macrophage function and its therapeutic effect in a mouse model of bleomycin-induced ILD (BLM-ILD). To this end, the phenotype of thioglycolate-induced murine peritoneal macrophages co-cultured with hMIKO-1 was examined. The mice were assigned to normal, BLM-alone, or BLM + hMIKO-1 groups, and hMIKO-1 (0.1 mg\/mouse) was administered intraperitoneally from day 0 to 14. The mice were sacrificed on day 28, and their lungs were evaluated by histological examination, collagen content, and gene expression levels. hMIKO-1 suppressed the polarization of murine macrophages to M2 predominance in vitro. The fibrosis score of lung pathology and lung collagen content of the BLM + hMIKO-1 group were significantly lower than those in the BLM-alone group. The expression levels of TNF-\u03b1, IL-6, IL-1\u03b2, F4\/80, and TIMP-1 in the lungs of the BLM + hMIKO-1 group were significantly lower than those in the BLM-alone group. These findings indicate that hMIKO-1 reduces lung fibrosis and may be a future therapeutic candidate for ILD treatment.<\/jats:p>","DOI":"10.3390\/ijms23179669","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T01:39:19Z","timestamp":1661737159000},"page":"9669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Human MIKO-1, a Hybrid Protein That Regulates Macrophage Function, Suppresses Lung Fibrosis in a Mouse Model of Bleomycin-Induced Interstitial Lung Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Takuya","family":"Kotani","sequence":"first","affiliation":[{"name":"Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Ikemoto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shogo","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Masutani","sequence":"additional","affiliation":[{"name":"Division of Central Laboratory, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tohru","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Thoracic Society (2000). 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