Xing X Du1, Yu Shi2, Ying Yang2, Ye Yu3, Hua G Lou2, Fang F Lv1, Zhi Chen2, Qiao Yang1. 1. Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 2. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 3. Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract
BACKGROUND & AIMS: Patients with acute-on-chronic liver failure (ACLF) usually exhibit defective monocyte function and excessive systemic inflammatory response. Interleukin-33 (IL-33) acts as a danger-associated molecular pattern (DAMP) to modulate immune response. However, the role of IL-33 in regulating monocyte function during hepatitis B-precipitated ACLF (HB-ACLF) in response to lipopolysaccharide (LPS) has not been clear. METHODS: In this study, the levels of IL-33/ST2 in blood and liver samples collected from patients with HB-ACLF, chronic hepatitis B (CHB) and normal controls and the associated of those findings with disease severity were analysed. HLA-DR and CD80 expression, phagocytosis capacity, cytokine secretion and MAP kinase activation induced by LPS were detected to explore the role of IL-33/ST2 signal in regulating monocyte function in patients. RESULTS: The expression levels of IL-33/ST2 were significantly increased in peripheral blood and livers of patients with HB-ACLF, as compared with patients with CHB and controls. It was found that serum IL-33 level was associated with severity of liver disease. Treatment with IL-33 on monocytes significantly increased HLA-DR, CCR2 and CD80 expression, enhanced LPS-stimulated TNF-α, IL-6 and IL-1β secretion, but did not affect the phagocytic capacity. Furthermore, IL-33 signalling enhanced the ERK1/2 activation of monocytes in response to LPS. CONCLUSIONS: DAMP molecular IL-33 augmented the 'storm' of monocytic inflammation in response to LPS through ERK1/2 activation during HB-ACLF.
BACKGROUND & AIMS:Patients with acute-on-chronic liver failure (ACLF) usually exhibit defective monocyte function and excessive systemic inflammatory response. Interleukin-33 (IL-33) acts as a danger-associated molecular pattern (DAMP) to modulate immune response. However, the role of IL-33 in regulating monocyte function during hepatitis B-precipitated ACLF (HB-ACLF) in response to lipopolysaccharide (LPS) has not been clear. METHODS: In this study, the levels of IL-33/ST2 in blood and liver samples collected from patients with HB-ACLF, chronic hepatitis B (CHB) and normal controls and the associated of those findings with disease severity were analysed. HLA-DR and CD80 expression, phagocytosis capacity, cytokine secretion and MAP kinase activation induced by LPS were detected to explore the role of IL-33/ST2 signal in regulating monocyte function in patients. RESULTS: The expression levels of IL-33/ST2 were significantly increased in peripheral blood and livers of patients with HB-ACLF, as compared with patients with CHB and controls. It was found that serum IL-33 level was associated with severity of liver disease. Treatment with IL-33 on monocytes significantly increased HLA-DR, CCR2 and CD80 expression, enhanced LPS-stimulated TNF-α, IL-6 and IL-1β secretion, but did not affect the phagocytic capacity. Furthermore, IL-33 signalling enhanced the ERK1/2 activation of monocytes in response to LPS. CONCLUSIONS: DAMP molecular IL-33 augmented the 'storm' of monocytic inflammation in response to LPS through ERK1/2 activation during HB-ACLF.
Authors: Ivan Ramirez-Moral; Dana C Blok; Jochem H Bernink; M Isabel Garcia-Laorden; Sandrine Florquin; Louis Boon; Cornelis Van't Veer; Matthias Mack; Simona Saluzzo; Sylvia Knapp; Hergen Spits; Alex F de Vos; Tom van der Poll Journal: J Pathol Date: 2021-01-19 Impact factor: 7.996