Liver international : official journal of the International Association for the Study of the Liver · 2010
Attenuation of toll-like receptor 2-mediated innate immune response in patients with alcoholic chronic liver disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Pimentel-Nunes Pedro, Roncon-Albuquerque Roberto, Gonçalves Nádia, Fernandes-Cerqueira Cátia, Cardoso Hélder, Bastos Rui Pedro, Marques Margarida, Marques Cristina, Alexandre Sarmento José, Costa-Santos Carlos, Macedo Guilherme, Pestana Manuel, Dinis-Ribeiro Mário, Leite-Moreira Adelino F
Аннотация
BACKGROUND: Alcoholic chronic liver disease (ACLD) is a common form of acquired immunodeficiency.
AIM: To evaluate ex vivo toll-like receptor (TLR) 2 and TLR4 innate immune response in stable ACLD.
METHODS: Blood was collected from 26 males with stable ACLD and from 17 controls. Serum was used for lipopolysaccharide (LPS), sCD14, LPS-binding protein (LBP), tumour necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-10) quantification. Peripheral blood monocytes (PBM) protein expression of TLR2 and TLR4 was determined by flow cytometry. Primary cultures of anti-CD11b positive selected PBM were stimulated with the TLR2/TLR6 ligand zymosan (Zym), with TLR2/TLR1 ligand lipopeptide (Lp) and with TLR4 ligand LPS. PBM TLR1, TLR2, TLR4, TLR6, MD2, CD14, TNF-alpha and IL-10 gene expression was evaluated by reverse transcription-polymerase chain reaction.
RESULTS: Stable ACLD patients showed increased circulating LPS (+22.5+/-4.1%), LBP (+60.6+/-12.2%) and sCD14 (+23.5+/-4.6%), with no differences in TNF-alpha and IL-10. Zym and Lp, but not LPS, induced TNF-alpha production by monocytes was blunted in ACLD (-66+/-20.4% Zym; -40.1+/-13.5% Lp; P<0.05). Basal TNF-alpha mRNA expression was decreased in PBM from ACLD patients (-50.1+/-21.0%; P<0.05), with no significant differences in the other studied genes. Results were similar in Child-Pugh A and B/C patients.
CONCLUSIONS: Patients with stable ACLD show an attenuation of TLR2-mediated innate immune response in PBM, which may represent an important mechanism for acquired immunodeficiency. This was neither related with decreased TLR2 or its co-receptors expression nor with impaired TLR4 activation, being already present in the early stages of disease.
AIM: To evaluate ex vivo toll-like receptor (TLR) 2 and TLR4 innate immune response in stable ACLD.
METHODS: Blood was collected from 26 males with stable ACLD and from 17 controls. Serum was used for lipopolysaccharide (LPS), sCD14, LPS-binding protein (LBP), tumour necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-10) quantification. Peripheral blood monocytes (PBM) protein expression of TLR2 and TLR4 was determined by flow cytometry. Primary cultures of anti-CD11b positive selected PBM were stimulated with the TLR2/TLR6 ligand zymosan (Zym), with TLR2/TLR1 ligand lipopeptide (Lp) and with TLR4 ligand LPS. PBM TLR1, TLR2, TLR4, TLR6, MD2, CD14, TNF-alpha and IL-10 gene expression was evaluated by reverse transcription-polymerase chain reaction.
RESULTS: Stable ACLD patients showed increased circulating LPS (+22.5+/-4.1%), LBP (+60.6+/-12.2%) and sCD14 (+23.5+/-4.6%), with no differences in TNF-alpha and IL-10. Zym and Lp, but not LPS, induced TNF-alpha production by monocytes was blunted in ACLD (-66+/-20.4% Zym; -40.1+/-13.5% Lp; P<0.05). Basal TNF-alpha mRNA expression was decreased in PBM from ACLD patients (-50.1+/-21.0%; P<0.05), with no significant differences in the other studied genes. Results were similar in Child-Pugh A and B/C patients.
CONCLUSIONS: Patients with stable ACLD show an attenuation of TLR2-mediated innate immune response in PBM, which may represent an important mechanism for acquired immunodeficiency. This was neither related with decreased TLR2 or its co-receptors expression nor with impaired TLR4 activation, being already present in the early stages of disease.
Предметные рубрики MeSH
Acute-Phase ProteinsCarrier ProteinsCase-Control StudiesCells, CulturedChronic DiseaseDown-RegulationGene Expression ProfilingHumansImmunity, InnateInterleukin-10Leukocytes, MononuclearLipopeptidesLipopolysaccharide ReceptorsLipopolysaccharidesLiver Diseases, AlcoholicMaleMembrane GlycoproteinsMiddle AgedPortugalRNA, MessengerToll-Like Receptor 2Toll-Like Receptor 4Tumor Necrosis Factor-alphaZymosanLipopolysaccharide-Binding Protein