Skip to main content
main-content

08.05.2020 | Original Article

Role of cell autophagy in the generation of IgM and hepatic fibrosis in primary biliary cholangitis

Zeitschrift:
Clinical Rheumatology
Autoren:
Chaofeng Lian, Yun Zhao, Jinlei Sun, Liling Zhao, Fengchun Zhang
Wichtige Hinweise

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abstract

Objective

Autophagy in the immune and autoimmune diseases has been concerned more and more. We investigated the potential role of cell autophagy of B cells generating IgM in primary biliary cholangitis (PBC), and explored the relationship between the cell autophagy of hepatic stellate cells (HSCs) and hepatic fibrosis in PBC.

Methods

We examined the aggregation degree of microtubule-associated protein light chain 3II (LC3II) in B cells of PBC (n = 21), health control (HC, n = 15) and disease control (DC, n = 8, active hepatitis B). The expression level of p62/SQSTM1 (p62) in B cells was detected by flow cytometry. ELISA was adopted to detect the level of IgM in the B cell culture supernatant under the basal condition, activated condition(stimulated by pokeweed mitogen, PWM) and inhibited condition(inhibited by autophagy inhibitor, 3-methyladenine, 3-MA) respectively. We detected the expression of α-smooth muscle actin (α-SMA), the infiltration level of LC3II, transforming growth factor-β (TGF-β), platelet-derived growth factor-bb (PDGF-bb), and collagen I in the hepatic tissues of five PBC patients and two HC individuals.

Results

When B cells were stimulated and activated by PWM, the expression of p62 increased, and the mean fluorescence intensity (MFI, 2404.8 ± 689.0) of p62 in PBC was lower than that in HC (2966.8 ± 488.9,P = 0.0227). Under 3-MA treatment, the MFI expressed of p62 in B cells weakened. The reduction difference in PBC (466.4 ± 214.9) was smaller than that in HC (1166.6 ± 231.2, P = 0.0000) and DC (1184.8 ± 197.7, P = 0.0001). The level of generating IgM in the PBC group was obviously higher than that in the HC group (65.7 ± 15.4 vs. 49.5 ± 20.4 ng/ml, P = 0.0357). Before and after B cells were treated with 3-MA, the peak level of IgM did not significantly diminish in PBC and DC (65.7 ± 15.4 vs. 59.6 ± 18.7 ng/ml, P = 0.2965; 50.1 ± 17.4 vs. 48.4 ± 12.3 ng/ml, P = 0.8336). The immunohistochemical result revealed that the expression level of collagen I, α-SMA, TGF-β and PDGF-bb in PBC was higher than that in HC, but the expression of LC3II was lower. Similarly, immunofluorescence assay revealed that the fluorescence intensity of collagen I was higher but LC3II was lower in PBC than that in HC.

Conclusion

The high level autophagy of B cells from PBC patients is one important factor to synthesize and secrete IgM. Hepatic fibrosis of PBC is probably associated with the weakened autophagy of HSCs.
Key Points
• High-level autophagy of B cells in PBC patients is an important factor to synthesize and secrete IgM.
• Pro-fibrogenic cytokines in PBC influence the increase of collagen-I through HSC autophagy, and promote the occurrence and development of hepatic fibrosis.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

Weitere Produktempfehlungen anzeigen
Literatur
Über diesen Artikel
  1. Sie können e.Med Innere Medizin 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

Neu im Fachgebiet Innere Medizin

Meistgelesene Bücher aus der Inneren Medizin

2017 | Buch

Rheumatologie aus der Praxis

Entzündliche Gelenkerkrankungen – mit Fallbeispielen

Dieses Fachbuch macht mit den wichtigsten chronisch entzündlichen Gelenk- und Wirbelsäulenerkrankungen vertraut. Anhand von über 40 instruktiven Fallbeispielen werden anschaulich diagnostisches Vorgehen, therapeutisches Ansprechen und der Verlauf …

Herausgeber:
Rudolf Puchner

2016 | Buch

Ambulant erworbene Pneumonie

Was, wann, warum – Dieses Buch bietet differenzierte Diagnostik und Therapie der ambulant erworbenen Pneumonie zur sofortigen sicheren Anwendung. Entsprechend der neuesten Studien und Leitlinien aller wichtigen Fachgesellschaften.

Herausgeber:
Santiago Ewig

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin 

Bildnachweise