PMID- 15972949
OWN - NLM
STAT- MEDLINE
DCOM- 20050825
LR  - 20190608
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 167
IP  - 1
DP  - 2005 Jul
TI  - Inhibition of macrophage nuclear factor-kappaB leads to a dominant 
      anti-inflammatory phenotype that attenuates glomerular inflammation in vivo.
PG  - 27-37
AB  - Infiltrating macrophages (mphi) can cause injury or facilitate repair, depending 
      on how they are activated by the microenvironment. Studies in vitro have defined 
      the roles of individual cytokines and signaling pathways in activation, but 
      little is known about how macrophages integrate the multiple signals they receive 
      in vivo. We inhibited nuclear factor-kappaB in bone marrow-derived macrophages 
      (BMDMs) by using a recombinant adenovirus expressing dominant-negative IkappaB 
      (Ad-IkappaB). This re-orientated macrophage activation so they became profoundly 
      anti-inflammatory in settings where they would normally be classically activated. 
      In vitro, the lipopolysaccharide-induced nitric oxide, interleukin-12, and tumor 
      necrosis factor-alpha synthesis was abrogated while interleukin-10 synthesis 
      increased. In vivo, fluorescently labeled BMDMs transduced with Ad-IkappaB and 
      injected into the renal artery significantly reduced inducible nitric oxide 
      synthase and MHC class II expression when activated naturally in glomeruli of 
      rats with nephrotoxic nephritis. Furthermore, although they only comprised 15% of 
      glomerular macrophages, their presence significantly reduced glomerular 
      infiltration and activation of host macrophages. Injury in nephrotoxic nephritis 
      was also decreased when assessed morphologically and by severity of albuminuria. 
      The results demonstrate the power of Ad-IkappaB-transduced BMDMs to inhibit 
      injury when activated by acute immune-mediated inflammation within the 
      glomerulus.
FAU - Wilson, Heather M
AU  - Wilson HM
AD  - Department of Medicine and Therapeutics, University of Aberdeen, Institute of 
      Medical Sciences, Foresterhill, Aberdeen, Scotland, AB25 2ZD, UK. 
      h.m.wilson@abdn.ac.uk
FAU - Chettibi, Salah
AU  - Chettibi S
FAU - Jobin, Christian
AU  - Jobin C
FAU - Walbaum, David
AU  - Walbaum D
FAU - Rees, Andrew J
AU  - Rees AJ
FAU - Kluth, David C
AU  - Kluth DC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (NF-kappa B)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells
MH  - Electrophoretic Mobility Shift Assay
MH  - Flow Cytometry
MH  - In Vitro Techniques
MH  - Inflammation/immunology/*prevention & control
MH  - Interleukin-10/immunology
MH  - Kidney Glomerulus/*immunology/pathology
MH  - Macrophage Activation/immunology
MH  - Macrophages/*immunology
MH  - NF-kappa B/genetics/*immunology
MH  - Nephritis/immunology/pathology/*prevention & control
MH  - Phenotype
MH  - Rats
MH  - Transduction, Genetic
PMC - PMC1603438
EDAT- 2005/06/24 09:00
MHDA- 2005/08/27 09:00
PMCR- 2006/01/01
CRDT- 2005/06/24 09:00
PHST- 2005/06/24 09:00 [pubmed]
PHST- 2005/08/27 09:00 [medline]
PHST- 2005/06/24 09:00 [entrez]
PHST- 2006/01/01 00:00 [pmc-release]
AID - S0002-9440(10)62950-1 [pii]
AID - 10.1016/s0002-9440(10)62950-1 [doi]
PST - ppublish
SO  - Am J Pathol. 2005 Jul;167(1):27-37. doi: 10.1016/s0002-9440(10)62950-1.