2 research outputs found
TNFα-stimulated gene-6 (TSG6) activates macrophage phenotype transition to prevent inflammatory lung injury
TNFα-stimulated gene-6 (TSG6), a 30-kDa protein generated by activated
macrophages, modulates inflammation; however, its mechanism
of action and role in the activation of macrophages are not fully understood.
Here we observed markedly augmented LPS-induced inflammatory
lung injury and mortality in TSG6−/− mice compared with WT
(TSG6+/+) mice. Treatment of mice with intratracheal instillation of
TSG6 prevented LPS-induced lung injury and neutrophil sequestration,
and increased survival in mice. We found that TSG6 inhibited the
association of TLR4withMyD88, thereby suppressing NF-κB activation.
TSG6 also prevented the expression of proinflammatory proteins (iNOS,
IL-6, TNFα, IL-1β, and CXCL1) while increasing the expression of antiinflammatory
proteins (CD206, Chi3l3, IL-4, and IL-10) in macrophages.
This shift was associated with suppressed activation of proinflammatory
transcription factors STAT1 and STAT3. In addition, we observed
that LPS itself up-regulated the expression of TSG6 in TSG6+/+
mice, suggesting an autocrine role for TSG6 in transitioning macrophages.
Thus, TSG6 functions by converting macrophages from a
proinflammatory to an anti-inflammatory phenotype secondary to
suppression of TLR4/NF-κB signaling and STAT1 and STAT3 activation