title: T cells and lung injury. Impact of rapamycin.
abstract: Acute lung injury (ALI) is characterized by pulmonary inflammation and edema. Innate immune cells (e.g., neutrophils and macrophages) are major contributors to inflammation in ALI. Less is known regarding the role of T cells. We examined the effects of rapamycin on inflammation in a LPS-induced murine model of ALI. Rapamycin was administered before and after initiation of injury. Inflammatory parameters, including bronchoalveolar lavage cell counts, T cell surface markers (i.e., cytotoxic T lymphocyte antigen 4 [CTLA4] and fork head-winged helix transcription factor [Foxp3]), T cell activation (CD69), IL-6, and IL-10 were analyzed. Rapamycin significantly decreased inflammatory parameters and decreased Foxp3, CTLA4, and CD69 in CD4(+) T cells. Rapamycin administration before or after the onset of lung injury, as well as systemically or by pulmonary routes, ameliorates inflammation in ALI.
authors.affiliation: 1 Division of Pulmonary and Critical Medicine, Department of Medicine, University of California, San Diego, California; and.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Ko-Wei
authors.initials: KW
authors.lastname: Lin
authors.forename: Jinghong
authors.initials: J
authors.lastname: Li
authors.forename: Halvor S
authors.initials: HS
authors.lastname: McGee
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kwan
authors.forename: David L
authors.initials: DL
authors.lastname: Perkins
authors.forename: Patricia W
authors.initials: PW
authors.lastname: Finn
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D060908:CTLA-4 Antigen / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D020123:Sirolimus / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C482199:lipopolysaccharide, E coli O55-B5; D020123:Sirolimus
keywords: CTLA4; LPS; T cells; acute lung injury; rapamycin