title: Mannose-binding lectin inhibits monocyte proliferation through transforming growth factor-β1 and p38 signaling pathways.
abstract: Mannose-binding lectin (MBL), a plasma C-type lectin, plays an important role in innate immunity. However, the interaction, and the consequences of it, between MBL and the immune system remain ill defined. We have investigated the contributing mechanisms and effects of MBL on the proliferation of human monocytes. At lower concentrations (≤4 μg/ml) MBL was shown to partially enhance monocyte proliferation. By contrast, at higher concentrations (8-20 μg/ml) of MBL, cell proliferation was markedly attenuated. MBL-induced growth inhibition was associated with G0/G1 arrest, down-regulation of cyclin D1/D3, cyclin-dependent kinase (Cdk) 2/Cdk4 and up-regulation of the Cdk inhibitory protein Cip1/p21. Additionally, MBL induced apoptosis, and did so through caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavage. Moreover, transforming growth factor (TGF)-β1 levels increased in the supernatants of MBL-stimulated monocyte cultures. We also found that MBL-dependent inhibition of monocyte proliferation could be reversed by the TGF-β receptor antagonist SB-431542, or by anti-TGF-β1 antibody, or by the mitogen-activated protein kinase (MAPK) inhibitors specific for p38 (SB203580), but not ERK (U0126) or JNK (SP600125). Thus, at high concentrations, MBL can affect the immune system by inhibiting monocyte proliferation, which suggests that MBL may exhibit anti-inflammatory effects.
authors.affiliation: Department of Immunology, Southern Medical University, Guangzhou, Guangdong, China ; Department of Microbiology and Immunology, School of Basic Medicine, Guangdong Medical College, Dongguan, Guangdong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: A-De
authors.initials: AD
authors.lastname: Chen
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Lei
authors.forename: Gui-Qiu
authors.initials: GQ
authors.lastname: Shan
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Lu
authors.forename: Zheng-Liang
authors.initials: ZL
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059585:G1 Phase Cell Cycle Checkpoints; D005786:Gene Expression Regulation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D037601:Mannose-Binding Lectin / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D007093:Imidazoles; D037601:Mannose-Binding Lectin; D011725:Pyridines; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; C093642:SB 203580
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