{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:00:31Z","timestamp":1784091631188,"version":"3.55.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations of the tumor suppressor genes, tuberous sclerosis complex (TSC) 1 or TSC2. LAM affects women almost exclusively, and it is characterized by neoplastic growth of atypical smooth muscle\u2013like TSC2-null LAM cells in the pulmonary interstitium, cystic destruction of lung parenchyma, and progressive decline in lung function. In this study, we hypothesized that TSC2-null lesions promote a proinflammatory environment, which contributes to lung parenchyma destruction. Using a TSC2-null female murine LAM model, we demonstrate that TSC2-null lesions promote alveolar macrophage accumulation, recruitment of immature multinucleated cells, an increased induction of proinflammatory genes, nitric oxide (NO) synthase 2, IL-6, chemokine (C-C motif) ligand 2 (CCL2)\/monocyte chemotactic protein 1 (MCP1), chemokine (C-X-C motif) ligand 1 (CXCL1)\/keratinocyte chemoattractant (KC), and up-regulation of IL-6, KC, MCP-1, and transforming growth factor-\u03b21 levels in bronchoalveolar lavage fluid. Bronchoalveolar lavage fluid also contained an increased level of surfactant protein (SP)-D, but not SP-A, significant reduction of SP-B levels, and a resultant increase in alveolar surface tension. Consistent with the growth of TSC2-null lesions, NO levels were also increased and, in turn, modified SP-D through S-nitrosylation, forming S-nitrosylated SP-D, a known consequence of lung inflammation. Progressive growth of TSC2-null lesions was accompanied by elevated levels of matrix metalloproteinase-3 and -9. This report demonstrates a link between growth of TSC2-null lesions and inflammation-induced surfactant dysfunction that might contribute to lung destruction in LAM.<\/jats:p>","DOI":"10.1165\/rcmb.2014-0224oc","type":"journal-article","created":{"date-parts":[[2014,12,4]],"date-time":"2014-12-04T16:00:17Z","timestamp":1417708817000},"page":"96-104","source":"Crossref","is-referenced-by-count":21,"title":["Surfactant Dysfunction and Lung Inflammation in the Female Mouse Model of Lymphangioleiomyomatosis"],"prefix":"10.1093","volume":"53","author":[{"given":"Elena N.","family":"Atochina-Vasserman","sequence":"first","affiliation":[{"name":"Airway Biology Initiative and"},{"name":"Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Jiang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Abramova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thea N.","family":"Golden","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sims","sequence":"additional","affiliation":[{"name":"Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melane L.","family":"James","sequence":"additional","affiliation":[{"name":"Airway Biology Initiative and"},{"name":"Pulmonary, Allergy, and Critical Care 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