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2014 ; 32
(6
): 1616-28
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Interleukin 6 mediates the therapeutic effects of adipose-derived stromal/stem
cells in lipopolysaccharide-induced acute lung injury
#MMPMID24449042
Zhang S
; Danchuk SD
; Bonvillain RW
; Xu B
; Scruggs BA
; Strong AL
; Semon JA
; Gimble JM
; Betancourt AM
; Sullivan DE
; Bunnell BA
Stem Cells
2014[Jun]; 32
(6
): 1616-28
PMID24449042
show ga
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.
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