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Article: Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin

TitleAutophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin
Authors
Issue Date2015
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cddis/index.html
Citation
Cell Death & Disease, 2015, v. 6, p. e1942 How to Cite?
AbstractThe plasticity of tumour-associated macrophages (TAMs) has implicated an influential role in hepatocellular carcinoma (HCC). Repolarisation of TAM towards M1 phenotype characterises an immune-competent microenvironment that favours tumour regression. To investigate the role and mechanism of TAM repolarisation in suppression of HCC by a natural compound baicalin, Orthotopic HCC implantation model was used to investigate the effect of baicalin on HCC; liposome-clodronate was introduced to suppress macrophage populations in mice; bone marrow-derived monocytes (BMDMs) were induced to unpolarised, M1-like, M2-like macrophages and TAM using different conditioned medium. We observed that oral administration of baicalin (50 mg/kg) completely blocked orthotopic growth of implanted HCC. Suppression of HCC by baicalin was diminished when mice macrophage was removed by clodronate treatment. Baicalin induced repolarisation of TAM to M1-like phenotype without specific toxicity to either phenotype of macrophages. Baicalin initiated TAM reprogramming to M1-like macrophage, and promoted pro-inflammatory cytokines production. Co-culturing of HCC cells with baicalin-treated TAMs resulted in reduced proliferation and motility in HCC. Baicalin had minimal effect on derivation of macrophage polarisation factors by HCC cells, while directly induced repolarisation of TAM and M2-like macrophage. This effect was associated with elevated autophagy, and transcriptional activation of RelB/p52 pathway. Suppression of autophagy or RelB abolished skewing of baicalin-treated TAM. Autophagic degradation of TRAF2 in baicalin-treated TAM might be responsible for RelB/p52 activation. Our findings unveil the essential role of TAM repolarisation in suppressive effect of baicalin on HCC, which requires autophagy-associated activation of RelB/p52.
DescriptionOpen Access Journal
Persistent Identifierhttp://hdl.handle.net/10722/221536
ISSN
2015 Impact Factor: 5.378
2015 SCImago Journal Rankings: 2.484
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorTAN, HY-
dc.contributor.authorWang, N-
dc.contributor.authorMan, K-
dc.contributor.authorTsao, GSW-
dc.contributor.authorChe, CM-
dc.contributor.authorFeng, Y-
dc.date.accessioned2015-11-30T03:32:49Z-
dc.date.available2015-11-30T03:32:49Z-
dc.date.issued2015-
dc.identifier.citationCell Death & Disease, 2015, v. 6, p. e1942-
dc.identifier.issn2041-4889-
dc.identifier.urihttp://hdl.handle.net/10722/221536-
dc.descriptionOpen Access Journal-
dc.description.abstractThe plasticity of tumour-associated macrophages (TAMs) has implicated an influential role in hepatocellular carcinoma (HCC). Repolarisation of TAM towards M1 phenotype characterises an immune-competent microenvironment that favours tumour regression. To investigate the role and mechanism of TAM repolarisation in suppression of HCC by a natural compound baicalin, Orthotopic HCC implantation model was used to investigate the effect of baicalin on HCC; liposome-clodronate was introduced to suppress macrophage populations in mice; bone marrow-derived monocytes (BMDMs) were induced to unpolarised, M1-like, M2-like macrophages and TAM using different conditioned medium. We observed that oral administration of baicalin (50 mg/kg) completely blocked orthotopic growth of implanted HCC. Suppression of HCC by baicalin was diminished when mice macrophage was removed by clodronate treatment. Baicalin induced repolarisation of TAM to M1-like phenotype without specific toxicity to either phenotype of macrophages. Baicalin initiated TAM reprogramming to M1-like macrophage, and promoted pro-inflammatory cytokines production. Co-culturing of HCC cells with baicalin-treated TAMs resulted in reduced proliferation and motility in HCC. Baicalin had minimal effect on derivation of macrophage polarisation factors by HCC cells, while directly induced repolarisation of TAM and M2-like macrophage. This effect was associated with elevated autophagy, and transcriptional activation of RelB/p52 pathway. Suppression of autophagy or RelB abolished skewing of baicalin-treated TAM. Autophagic degradation of TRAF2 in baicalin-treated TAM might be responsible for RelB/p52 activation. Our findings unveil the essential role of TAM repolarisation in suppressive effect of baicalin on HCC, which requires autophagy-associated activation of RelB/p52.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cddis/index.html-
dc.relation.ispartofCell Death & Disease-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleAutophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin-
dc.typeArticle-
dc.identifier.emailWang, N: ckwang@hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailChe, CM: cmche@hku.hk-
dc.identifier.emailFeng, Y: yfeng@hku.hk-
dc.identifier.authorityWang, N=rp02075-
dc.identifier.authorityMan, K=rp00417-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityChe, CM=rp00670-
dc.identifier.authorityFeng, Y=rp00466-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/cddis.2015.271-
dc.identifier.pmid26492375-
dc.identifier.pmcidPMC4632300-
dc.identifier.hkuros256155-
dc.identifier.volume6-
dc.identifier.spagee1942-
dc.identifier.epagee1942-
dc.publisher.placeUnited Kingdom-

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