PPAR γ Deficiency Exacerbates Fibrotic Response to Mycobacteria Peptide in Murine Sarcoidosis Model.

PPARγ Deficiency Exacerbates Fibrotic Response to Mycobacteria Peptide in Murine Sarcoidosis Model. Am J Respir Cell Mol Biol. 2019 Feb 11;: Authors: Malur A, Mohan A, Barrington RA, Leffler N, Malur A, Muller-Borer B, Murray G, Kew K, Zhou C, Russell J, Jones JL, Wingard CJ, Barna BP, Thomassen MJ Abstract We established a murine model of multiwall carbon nanotube (MWCNT)-elicited chronic granulomatous disease which bears similarities to human sarcoidosis pathology including alveolar macrophage deficiency of peroxisome-proliferator-activated receptor gamma (PPARγ). Because lymphocyte reactivity to mycobacterial antigens has been reported in sarcoidosis, we hypothesized that addition of mycobacterial Early Secreted Antigenic Target Protein 6 (ESAT-6) to MWCNT might exacerbate pulmonary granulomatous pathology. MWCNT with or without ESAT-6 peptide-14 were instilled by oropharyngeal route into macrophage-specific PPARγ KO or wild-type mice. Controls received PBS or ESAT-6. Lung tissues, bronchoalveolar lavage (BAL) cells and fluid, were evaluated 60 days post instillation. PPARγ-KO mice receiving MWCNT+ESAT-6 had increased granulomas and significantly elevated fibrosis (trichrome staining) vs wild-type mice or PPARγ-KO mice receiving only MWCNT. Immunostaining of lung tissues noted elevated fibronectin and Siglec F expression on CD11c(+) infiltrating alveolar macrophages in the presence of MWCNT+ESAT-6 compared to MWCNT. Analyses ...
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research