PMID- 21098396
OWN - NLM
STAT- MEDLINE
DCOM- 20110321
LR  - 20211020
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 117
IP  - 4
DP  - 2011 Jan 27
TI  - Immunoglobulin light chains activate nuclear factor-kappaB in renal epithelial cells 
      through a Src-dependent mechanism.
PG  - 1301-7
LID - 10.1182/blood-2010-08-302505 [doi]
AB  - One of the major attendant complications of multiple myeloma is renal injury, 
      which contributes significantly to morbidity and mortality in this disease. 
      Monoclonal immunoglobulin free light chains (FLCs) are usually directly involved, 
      and tubulointerstitial renal injury and fibrosis are prominent histologic 
      features observed in myeloma. The present study examined the role of monoclonal 
      FLCs in altering the nuclear factor kappa light chain enhancer of activated B cells 
      (NF-kappaB) activity of renal epithelial cells. Human proximal tubule epithelial 
      cells exposed to 3 different human monoclonal FLCs demonstrated Src 
      kinase-dependent activation of the NF-kappaB pathway, which increased production of 
      monocyte chemoattractant protein-1 (MCP-1). Tyrosine phosphorylation of inhibitor 
      of kappaB kinases (IKKs) IKKalpha and IKKbeta and a concomitant increase in inhibitor of kappaB 
      (IkappaB) kinase activity in cell lysates were observed. Time-dependent, Src 
      kinase-dependent increases in serine and tyrosine phosphorylation of IkappaBalpha and 
      NF-kappaB activity were also demonstrated. Proteasome inhibition partially blocked 
      FLC-induced MCP-1 production. These findings fit into a paradigm characterized by 
      FLC-induced redox-signaling events that activated the canonical and atypical 
      (IKK-independent) NF-kappaB pathways to promote a proinflammatory, profibrotic renal 
      environment.
FAU - Ying, Wei-Zhong
AU  - Ying WZ
AD  - Division of Nephrology, Department of Medicine, Nephrology Research and Training 
      Center, Center for Free Radical Biology, University of Alabama, Birmingham, AL, 
      USA.
FAU - Wang, Pei-Xuan
AU  - Wang PX
FAU - Aaron, Kristal J
AU  - Aaron KJ
FAU - Basnayake, Kolitha
AU  - Basnayake K
FAU - Sanders, Paul W
AU  - Sanders PW
LA  - eng
GR  - P30 DK079337/DK/NIDDK NIH HHS/United States
GR  - R01 DK046199-17/DK/NIDDK NIH HHS/United States
GR  - R01 DK046199/DK/NIDDK NIH HHS/United States
GR  - I01 CX001326/CX/CSRD VA/United States
GR  - R01 DK46199/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20101122
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Boronic Acids)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Immunoglobulin Light Chains)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyrazines)
RN  - 42HK56048U (Tyrosine)
RN  - 69G8BD63PP (Bortezomib)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Boronic Acids/pharmacology
MH  - Bortezomib
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical
MH  - Epithelial Cells/*drug effects/metabolism
MH  - Humans
MH  - I-kappa B Kinase/metabolism
MH  - Immunoglobulin Light Chains/*pharmacology/physiology
MH  - Kidney/*drug effects/metabolism
MH  - NF-kappa B/*metabolism
MH  - Phosphorylation/drug effects
MH  - Pyrazines/pharmacology
MH  - Signal Transduction/drug effects
MH  - Tyrosine/metabolism
MH  - src-Family Kinases/metabolism/*physiology
PMC - PMC3056473
EDAT- 2010/11/26 06:00
MHDA- 2011/03/22 06:00
PMCR- 2012/01/27
CRDT- 2010/11/25 06:00
PHST- 2010/11/25 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2011/03/22 06:00 [medline]
PHST- 2012/01/27 00:00 [pmc-release]
AID - S0006-4971(20)58606-0 [pii]
AID - 2010/302505 [pii]
AID - 10.1182/blood-2010-08-302505 [doi]
PST - ppublish
SO  - Blood. 2011 Jan 27;117(4):1301-7. doi: 10.1182/blood-2010-08-302505. Epub 2010 
      Nov 22.