Deletion of c-FLIP from CD11b^hi Macrophages Prevents Development of Bleomycin-induced Lung Fibrosis.

ABSTRACT: Idiopathic pulmonary fibrosis is a progressive lung disease with complex pathophysiology and fatal prognosis. Macrophages (MΦ) contribute to the development of lung fibrosis; however, the underlying mechanisms and specific MΦ subsets involved remain unclear. During lung injury, two subsets of lung MΦ coexist: Siglec-F^hi resident alveolar MΦ and a mixed population of CD11b^hi MΦ that primarily mature from immigrating monocytes. Using a novel inducible transgenic system driven by a fragment of the human CD68 promoter, we targeted deletion of the antiapoptotic protein cellular FADD-like IL-1β-converting enzyme-inhibitory protein (c-FLIP) to CD11b^hi MΦ. Upon loss of c-FLIP, CD11b^hi MΦ became susceptible to cell death. Using this system, we were able t

SUBMITTER: McCubbrey AL 

PROVIDER: S-EPMC5941310 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature