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Cytosolic DNA Triggers Inflammasome Activation in Keratinocytes in Psoriatic Lesions，
82ra38 (2011); 3 Sci Transl Med
abstract :
The proinflammatory cytokine interleukin-1 (IL-1 ) plays a central role in the pathogenesis and the course
of inflammatory skin diseases, including psoriasis. Posttranscriptional activation of IL-1 is mediated by
inflammasomes; however, the mechanisms triggering IL-1 processing remain unknown. Recently, cytosolic
DNA has been identified as a danger signal that activates inflammasomes containing the DNA sensor AIM2. In
this study, we detected abundant cytosolic DNA and increased AIM2 expression in keratinocytes in psoriatic lesions
but not in healthy skin. In cultured keratinocytes, interferon- induced AIM2, and cytosolic DNA triggered the re-
lease of IL-1 via the AIM2 inflammasome. Moreover, the antimicrobial cathelicidin peptide LL-37, which can inter-
act with DNA in psoriatic skin, neutralized cytosolic DNA in keratinocytes and blocked AIM2 inflammasome
activation. Together, these data suggest that cytosolic DNA is an important disease-associated molecular pattern
that can trigger AIM2 inflammasome and IL-1 activation in psoriasis. Furthermore, cathelicidin LL-37 interfered
with DNA-sensing inflammasomes, which thereby suggests an anti-inflammatory function for this peptide. Thus,
our data reveal a link between the AIM2 inflammasome, cathelicidin LL-37, and autoinflammation in psoriasis,
providing new potential targets for the treatment of this chronic skin disease.
82ra38 (2011); 3 Sci Transl Med
abstract :
The proinflammatory cytokine interleukin-1 (IL-1 ) plays a central role in the pathogenesis and the course
of inflammatory skin diseases, including psoriasis. Posttranscriptional activation of IL-1 is mediated by
inflammasomes; however, the mechanisms triggering IL-1 processing remain unknown. Recently, cytosolic
DNA has been identified as a danger signal that activates inflammasomes containing the DNA sensor AIM2. In
this study, we detected abundant cytosolic DNA and increased AIM2 expression in keratinocytes in psoriatic lesions
but not in healthy skin. In cultured keratinocytes, interferon- induced AIM2, and cytosolic DNA triggered the re-
lease of IL-1 via the AIM2 inflammasome. Moreover, the antimicrobial cathelicidin peptide LL-37, which can inter-
act with DNA in psoriatic skin, neutralized cytosolic DNA in keratinocytes and blocked AIM2 inflammasome
activation. Together, these data suggest that cytosolic DNA is an important disease-associated molecular pattern
that can trigger AIM2 inflammasome and IL-1 activation in psoriasis. Furthermore, cathelicidin LL-37 interfered
with DNA-sensing inflammasomes, which thereby suggests an anti-inflammatory function for this peptide. Thus,
our data reveal a link between the AIM2 inflammasome, cathelicidin LL-37, and autoinflammation in psoriasis,
providing new potential targets for the treatment of this chronic skin disease.
版主小舟儿留言:
谢谢分享，希望楼主能够对本文献做一简要评述，供大家学习、讨论。
谢谢分享，希望楼主能够对本文献做一简要评述，供大家学习、讨论。
