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We evaluated the role of the endocannabinoid\/CB\n                    <jats:sub>1<\/jats:sub>\n                    R system and inducible nitric oxide synthase (iNOS) for dual\u2010target therapeutic strategy using human bronchoalveolar lavage fluid (BALF), lung samples from patients with HPS and controls, HPS\u2010PF patient\u2010derived lung fibroblasts, and bleomycin\u2010induced PF in pale ear mice (HPS1\n                    <jats:sup>ep\/ep<\/jats:sup>\n                    ). We found overexpression of CB\n                    <jats:sub>1<\/jats:sub>\n                    R and iNOS in fibrotic lungs of HPSPF patients and bleomycin\u2010infused pale ear mice. The endocannabinoid anandamide was elevated in BALF and negatively correlated with pulmonary function parameters in HPSPF patients and pale ear mice with bleomycin\u2010induced PF. Simultaneous targeting of CB\n                    <jats:sub>1<\/jats:sub>\n                    R and iNOS by MRI\u20101867 yielded greater antifibrotic efficacy than inhibiting either target alone by attenuating critical pathologic pathways. Moreover, MRI\u20101867 treatment abrogated bleomycin\u2010induced increases in lung levels of the profibrotic interleukin\u201011 via iNOS inhibition and reversed mitochondrial dysfunction via CB\n                    <jats:sub>1<\/jats:sub>\n                    R inhibition. Dual inhibition of CB\n                    <jats:sub>1<\/jats:sub>\n                    R and iNOS is an effective antifibrotic strategy for HPSPF.\n                  <\/jats:p>","DOI":"10.1002\/ctm2.471","type":"journal-article","created":{"date-parts":[[2021,7,4]],"date-time":"2021-07-04T10:41:02Z","timestamp":1625395262000},"source":"Crossref","is-referenced-by-count":37,"title":["CB\n                    <sub>1<\/sub>\n                    R and iNOS are distinct players promoting pulmonary fibrosis in Hermansky\u2013Pudlak syndrome"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-7253","authenticated-orcid":false,"given":"Resat","family":"Cinar","sequence":"first","affiliation":[{"name":"Section on Fibrotic Disorders National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Maryland USA"},{"name":"Laboratory of Physiologic Studies National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  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