Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity.
The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of...
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doaj-bb25e1f392af4a7b9278f9c7e8bd24082020-11-25T01:32:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01118e016073410.1371/journal.pone.0160734Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity.Shanshan XieLaura SpelminkMario CodemoKarthik SubramanianKatrin PütsepBirgitta Henriques-NormarkMarie OlliverThe traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy.http://europepmc.org/articles/PMC4986986?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shanshan Xie Laura Spelmink Mario Codemo Karthik Subramanian Katrin Pütsep Birgitta Henriques-Normark Marie Olliver |
spellingShingle |
Shanshan Xie Laura Spelmink Mario Codemo Karthik Subramanian Katrin Pütsep Birgitta Henriques-Normark Marie Olliver Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity. PLoS ONE |
author_facet |
Shanshan Xie Laura Spelmink Mario Codemo Karthik Subramanian Katrin Pütsep Birgitta Henriques-Normark Marie Olliver |
author_sort |
Shanshan Xie |
title |
Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity. |
title_short |
Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity. |
title_full |
Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity. |
title_fullStr |
Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity. |
title_full_unstemmed |
Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity. |
title_sort |
cinobufagin modulates human innate immune responses and triggers antibacterial activity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy. |
url |
http://europepmc.org/articles/PMC4986986?pdf=render |
work_keys_str_mv |
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