PMID- 20980264
OWN - NLM
STAT- MEDLINE
DCOM- 20110321
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 5
DP  - 2011 Feb 4
TI  - TNF-alpha induces macroautophagy and regulates MHC class II expression in human 
      skeletal muscle cells.
PG  - 3970-80
LID - 10.1074/jbc.M110.159392 [doi]
AB  - Macroautophagy, a homeostatic process that shuttles cytoplasmic constituents into 
      endosomal and lysosomal compartments, has recently been shown to deliver antigens 
      for presentation on major histocompatibility complex (MHC) class II molecules. 
      Skeletal muscle fibers show a high level of constitutive macroautophagy and 
      express MHC class II molecules upon immune activation. We found that tumor 
      necrosis factor-alpha (TNF-alpha), a monokine overexpressed in inflammatory myopathies, 
      led to a marked up-regulation of macroautophagy in skeletal myocytes. 
      Furthermore, TNF-alpha augmented surface expression of MHC class II molecules in 
      interferon-gamma (IFN-gamma)-treated myoblasts. The synergistic effect of TNF-alpha and IFN-gamma 
      on the induction of MHC class II surface expression was not reflected by higher 
      intracellular human leukocyte antigen (HLA)-DR levels and was reversed by 
      macroautophagy inhibition, suggesting that TNF-alpha facilitates antigen processing 
      via macroautophagy for more efficient MHC class II loading. Muscle biopsies from 
      patients with sporadic inclusion body myositis, a well defined myopathy with 
      chronic inflammation, showed that over 20% of fibers that contained 
      autophagosomes costained for MHC class II molecules and that more than 40% of 
      double-positive muscle fibers had contact with CD4(+) and CD8(+) immune cells. 
      These findings establish a mechanism through which TNF-alpha regulates both 
      macroautophagy and MHC class II expression and suggest that 
      macroautophagy-mediated antigen presentation contributes to the immunological 
      environment of the inflamed human skeletal muscle.
FAU - Keller, Christian W
AU  - Keller CW
AD  - Laboratory of Viral Immunobiology, Christopher H. Browne Center for Immunology 
      and Immune Diseases, The Rockefeller University, New York, New York 10065, USA.
FAU - Fokken, Claudia
AU  - Fokken C
FAU - Turville, Stuart G
AU  - Turville SG
FAU - Lunemann, Anna
AU  - Lunemann A
FAU - Schmidt, Jens
AU  - Schmidt J
FAU - Munz, Christian
AU  - Munz C
FAU - Lunemann, Jan D
AU  - Lunemann JD
LA  - eng
GR  - R01 CA101741/CA/NCI NIH HHS/United States
GR  - R01 CA108609/CA/NCI NIH HHS/United States
GR  - R01CA108609/CA/NCI NIH HHS/United States
GR  - R01CA101741/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101027
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigen Presentation
MH  - Autophagy/*drug effects
MH  - Gene Expression Regulation
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - Immunity
MH  - Inflammation
MH  - Interferon-gamma/pharmacology
MH  - Muscle Cells/*immunology
MH  - Muscle, Skeletal/cytology/*pathology
MH  - Muscular Diseases/pathology
MH  - Myositis/pathology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC3030397
EDAT- 2010/10/29 06:00
MHDA- 2011/03/22 06:00
PMCR- 2012/02/04
CRDT- 2010/10/29 06:00
PHST- 2010/10/29 06:00 [entrez]
PHST- 2010/10/29 06:00 [pubmed]
PHST- 2011/03/22 06:00 [medline]
PHST- 2012/02/04 00:00 [pmc-release]
AID - S0021-9258(20)54097-0 [pii]
AID - M110.159392 [pii]
AID - 10.1074/jbc.M110.159392 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Feb 4;286(5):3970-80. doi: 10.1074/jbc.M110.159392. Epub 2010 
      Oct 27.