Interleukin 6 mediates the therapeutic effects of adipose-derived stromal/stem cells in lipopolysaccharide-induced acute lung injury.
Adipose-derived stromal/stem cells (ASCs) have anti-inflammatory as well as immunosuppressive activities and are currently the focus of clinical trials for a number of inflammatory diseases. Acute lung injury (ALI) is an inflammatory condition of the lung for which standard treatment is mainly supportive due to lack of effective therapies. Our recent studies have demonstrated the ability of both human ASCs (hASCs) and mouse ASCs (mASCs) to attenuate lung damage and inflammation in a rodent model of lipopolysaccharide-induced ALI, suggesting that ASCs may also be beneficial in treating ALI. To better understand how ASCs may act in ALI and to elucidate the mechanism(s) involved in ASC modulation of lung inflammation, gene expression analysis was performed in ASC-treated (hASCs or mASCs) and control sham-treated lungs. The results revealed a dramatic difference between the expression of anti-inflammatory molecules by hASCs and mASCs. These data show that the beneficial effects of hASCs and mASCs in ALI may result from the production of different paracrine factors. Interleukin 6 (IL-6) expression in the mASC-treated lungs was significantly elevated as compared to sham-treated controls 20 hours after delivery of the cells by oropharyngeal aspiration. Knockdown of IL-6 expression in mASCs by RNA interference abrogated most of their therapeutic effects, suggesting that the anti-inflammatory properties of mASCs in ALI are explained, at least in part, by activation of IL-6 secretion.
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA; Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Shijia
S
Zhang
Svitlana D
SD
Danchuk
Ryan W
RW
Bonvillain
Beibei
B
Xu
Brittni A
BA
Scruggs
Amy L
AL
Strong
Julie A
JA
Semon
Jeffrey M
JM
Gimble
Aline M
AM
Betancourt
Deborah E
DE
Sullivan
Bruce A
BA
Bunnell
D055371:Acute Lung Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D000273:Adipose Tissue / Q000166:cytology*; D000418:Albumins / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D008810:Mice, Inbred C57BL; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D017154:Stromal Cells
D000418:Albumins; D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides
Acute lung injury; Adipose-derived stromal/stem cell; Interleukin 6; Mouse