Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

Wang, Mingyong; Chen, Yue; Zhang, Yani; Zhang, Liyun; Xiao, Lü; Chen, Zhengliang

doi:10.1038/cmi.2011.1

Cited by 69 publications

(66 citation statements)

References 60 publications

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“…The results of ELISA assay verified the decrease of IL-8 and CXCL1 in CRC cells treated with sTLR4/MD-2 complex (Figure 4C). These results of pro-inflammatory and migration cytokines were consistent with previous studies [37, 38]. Since these pro-inflammatory and migration cytokines constituted tumor microenvironment of CRC to affect tumor progression [18], it was suggested in our study that sTLR4/MD-2 complex can inhibit tumor progress (Figure 5A) whereas sTLR4 or MD-2 alone could not inhibit tumor progress as effectively as sTLR4/MD-2 complex.…”

Section: Discussionsupporting

confidence: 92%

sTLR4/MD-2 complex inhibits colorectal cancer in vitro and in vivo by targeting LPS

et al. 2016

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Colorectal cancer (CRC) is aggressive and associated with TLR4-MD-2 signaling. Toll-like receptor 4 (TLR4) and myeloid differentiation protein 2 (MD-2) were highly expressed in human CRC. The soluble form of extracellular TLR4 domain (sTLR4) and MD-2 may have important roles in binding lipopolysaccharide (LPS). In this study, sTLR4 and MD-2 protein and prepared sTLR4/MD-2 complex were synthesized successfully to restrain LPS-TLR4/MD-2 activation by competing with cellular membrane TLR4 for binding LPS. The sTLR4/MD-2 complex can significantly attenuate LPS induced pro-inflammatory and migration cytokine production in vitro and in vivo, and inhibit the effect of LPS on the cell cycle, migration and invasion of human CRC cells in vitro. Administration of sTLR4/MD-2 complex protected mice from tumor both in xenograft and implantation metastasis model. The sTLR4/MD-2 complex treated mice had smaller tumor, less body weight loss and lower expression of inflammatory cytokines. Here, the azoxymethane/dextran sulfate sodium salt (AOM/DSS) murine model was used as an experimental platform to simulate the physiological and pathological processes of cancers associated with chronic intestinal inflammation. AOM/DSS-induced tumors were inhibited in mice treated by sTLR4/MD-2 complex. It is demonstrated in our study that sTLR4/MD-2 complex could inhibit CRC by competing with binding LPS, raising the complex's possibility of a new prevention agent against CRC.

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Section: Discussionsupporting

confidence: 92%

sTLR4/MD-2 complex inhibits colorectal cancer in vitro and in vivo by targeting LPS

et al. 2016

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“…[33] recently showed that recombinant MBL could interact with TLR4 and MD-2. More recently, we proved that MBL could bind to TLR4 directly, and suppress LPS-/TLR-mediated biological function [22]. The finding of an inhibitory effect of MBL on C. albicans -induced immune responses of human macrophages through TLR2 and TLR4 in this study further demonstrated the versatile ability in immune regulation of this member of the collectin family.…”

Section: Discussionsupporting

confidence: 67%

“…We have proved that MBL could bind to TLR4 directly, and suppress LPS-/TLR-mediated biological function [22]. TLR4 is the binding site (ligand) for MBL expressed on THP-1 cells.…”

Section: Resultsmentioning

confidence: 88%

“…[30] reported calcium-dependent MBL binding to autogeneic B lymphocytes, monocytes and imMDCs via its C-type lectin-binding site. More recently, we also proved that MBL bound to human THP-1 monocytes in calcium-dependent manner [22]. To study the possible mechanism of MBL's effect on the interaction between HK Candida cells and PMA-activated THP-1 cells, the experiments of MBL binding to PMA-activated THP-1 cells were performed.…”

Section: Discussionmentioning

confidence: 98%

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Mannan-Binding Lectin Inhibits Candida albicans-Induced Cellular Responses in PMA-Activated THP-1 Cells through Toll-Like Receptor 2 and Toll-Like Receptor 4

Wang

Wang²,

Jiao³

et al. 2013

PLoS ONE

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Background Candida albicans (C. albicans), the most common human fungal pathogen, can cause fatal systemic infections under certain circumstances. Mannan-binding lectin (MBL),a member of the collectin family in the C-type lectin superfamily, is an important serum component associated with innate immunity. Toll-like receptors (TLRs) are expressed extensively, and have been shown to be involved in C. albicans-induced cellular responses. We first examined whether MBL modulated heat-killed (HK) C. albicans-induced cellular responses in phorbol 12-myristate 13-acetate (PMA)-activated human THP-1 macrophages. We then investigated the possible mechanisms of its inhibitory effect.Methodology/Principal FindingEnzyme-linked immunosorbent assay (ELISA) and reverse transcriptasepolymerase chain reaction (RT-PCR) analysis showed that MBL at higher concentrations (10–20 µg/ml) significantly attenuated C. albicans-induced chemokine (e.g., IL-8) and proinflammatory cytokine (e.g., TNF-α) production from PMA-activated THP-1 cells at both protein and mRNA levels. Electrophoretic mobility shift assay (EMSA) and Western blot (WB) analysis showed that MBL could inhibit C. albicans-induced nuclear factor-κB (NF-κB) DNA binding and its translocation in PMA-activated THP-1 cells. MBL could directly bind to PMA-activated THP-1 cells in the presence of Ca2+, and this binding decreased TLR2 and TLR4 expressions in C. albicans-induced THP-1 macrophages. Furthermore, the binding could be partially inhibited by both anti-TLR2 monoclonal antibody (clone TL2.1) and anti-TLR4 monoclonal antibody (clone HTA125). In addition, co-immunoprecipitation experiments and microtiter wells assay showed that MBL could directly bind to the recombinant soluble form of extracellular TLR2 domain (sTLR2) and sTLR4.Conclusions/SignificanceOur study demonstrates that MBL can affect proinflammatory cytokine and chemokine expressions by modifying C. albicans-/TLR-signaling pathways. This study supports an important role for MBL on the regulation of C. albicans-induced cellular responses.

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“…The vast majority of studies indicate that MBL inhibits proinflammatory cytokine production (24,25,(38)(39)(40). Contradicting results, however, depending on the level of recombinant MBL or the experimental setup used, have been published (41)(42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

Mannose-Binding Lectin Is Required for the Effective Clearance of Apoptotic Cells by Adipose Tissue Macrophages During Obesity

et al. 2014

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Obesity is accompanied by the presence of chronic low-grade inflammation manifested by infiltration of macrophages into adipose tissue. Mannose-binding lectin (MBL), a soluble mediator of innate immunity, promotes phagocytosis and alters macrophage function. To assess the function of MBL in the development of obesity, we studied wild-type and MBL−/− mice rendered obese using a high-fat diet (HFD). Whereas no gross morphological differences were observed in liver, an HFD provoked distinct changes in the adipose tissue morphology of MBL−/− mice. In parallel with increased adipocyte size, MBL−/− mice displayed an increased influx of macrophages into adipose tissue. Macrophages were polarized toward an alternatively activated phenotype known to modulate apoptotic cell clearance. MBL deficiency also significantly increased the number of apoptotic cells in adipose tissue. Consistent with these observations, recombinant MBL enhanced phagocytic capacity of the stromal vascular fraction isolated from adipose tissue and modulated uptake of apoptotic adipocytes by macrophages. Despite changes in macrophage abundance and polarity, the absence of MBL did not affect systemic insulin resistance. Finally, in humans, lower levels of circulating MBL were accompanied by enhanced macrophage influx in subcutaneous adipose tissue. We propose a novel role for MBL in the recognition and clearance of apoptotic adipocytes during obesity.

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Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

Cited by 69 publications

References 60 publications

sTLR4/MD-2 complex inhibits colorectal cancer in vitro and in vivo by targeting LPS

sTLR4/MD-2 complex inhibits colorectal cancer in vitro and in vivo by targeting LPS

Mannan-Binding Lectin Inhibits Candida albicans-Induced Cellular Responses in PMA-Activated THP-1 Cells through Toll-Like Receptor 2 and Toll-Like Receptor 4

Mannose-Binding Lectin Is Required for the Effective Clearance of Apoptotic Cells by Adipose Tissue Macrophages During Obesity

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