Deepa Rana1, Ajay Duseja2, Radha K Dhiman2, Yogesh Chawla2, Sunil K Arora3. 1. Department of Immunopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India. 2. Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. 3. Department of Immunopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India. skarora_in@yahoo.com.
Abstract
PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is characterized by the presence of elevated circulating endotoxin levels. The continuous presence of endotoxin might be responsible for inducing activation of the innate immune system resulting in chronic sub-clinical inflammation. This study examines the status of dendritic cells (DCs), an important component of innate immune system, in patients with NAFLD. METHODS: Effect of lipopolysaccharide (LPS) stimulation on maturation and activation of monocyte derived dendritic cells (mo-DCs) was evaluated in ten patients with NAFLD using flow cytometry, endocytosis assay, cytokine assay and mixed leukocyte reaction. RESULTS: Although the frequency of mo-DCs in NAFLD patients was similar to that of healthy controls, there was no upregulation in levels of HLA-DR, CD83, CD80 and CD86 on their surface in response to LPS stimulation ex vivo. Although the mo-DC from patients had higher endocytosing and lower allostimulatory capacities as compared to healthy controls indicating maturation defects yet they secreted significantly high amount of TNF-α and IL-6 suggesting higher activation state. CONCLUSIONS: Our results indicate that DCs in patients with NAFLD exhibit immature yet functionally activated phenotype in response to LPS stimulation as they secrete inflammatory cytokines which further contribute in exacerbating the symptoms. Inefficient antigen presentation in these patients might add another parameter while looking at the severity of disease.
PURPOSE:Nonalcoholic fatty liver disease (NAFLD) is characterized by the presence of elevated circulating endotoxin levels. The continuous presence of endotoxin might be responsible for inducing activation of the innate immune system resulting in chronic sub-clinical inflammation. This study examines the status of dendritic cells (DCs), an important component of innate immune system, in patients with NAFLD. METHODS: Effect of lipopolysaccharide (LPS) stimulation on maturation and activation of monocyte derived dendritic cells (mo-DCs) was evaluated in ten patients with NAFLD using flow cytometry, endocytosis assay, cytokine assay and mixed leukocyte reaction. RESULTS: Although the frequency of mo-DCs in NAFLD patients was similar to that of healthy controls, there was no upregulation in levels of HLA-DR, CD83, CD80 and CD86 on their surface in response to LPS stimulation ex vivo. Although the mo-DC from patients had higher endocytosing and lower allostimulatory capacities as compared to healthy controls indicating maturation defects yet they secreted significantly high amount of TNF-α and IL-6 suggesting higher activation state. CONCLUSIONS: Our results indicate that DCs in patients with NAFLD exhibit immature yet functionally activated phenotype in response to LPS stimulation as they secrete inflammatory cytokines which further contribute in exacerbating the symptoms. Inefficient antigen presentation in these patients might add another parameter while looking at the severity of disease.
Authors: Alison L Harte; Nancy F da Silva; Steven J Creely; Kirsty C McGee; Thomas Billyard; Elham M Youssef-Elabd; Gyanendra Tripathi; Esmat Ashour; Mohga S Abdalla; Hayat M Sharada; Ashraf I Amin; Alastair D Burt; Sudhesh Kumar; Christopher P Day; Philip G McTernan Journal: J Inflamm (Lond) Date: 2010-03-30 Impact factor: 4.981