PMID- 9317146
OWN - NLM
STAT- MEDLINE
DCOM- 19971021
LR  - 20220408
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 159
IP  - 7
DP  - 1997 Oct 1
TI  - Interaction of IgA with Fc alpha receptors of human mesangial cells activates 
      transcription factor nuclear factor-kappa B and induces expression and synthesis 
      of monocyte chemoattractant protein-1, IL-8, and IFN-inducible protein 10.
PG  - 3474-82
AB  - The mechanisms of glomerular damage in IgA nephropathy remain undefined. 
      Mesangial cells (MC) possess Fc receptors for IgA (Fc alpha R), and their 
      occupancy triggers cytokine expression, cell proliferation, and extracellular 
      matrix synthesis. In cultured human MC we examined the effects of soluble IgA 
      aggregates (AIgA) on the activation of nuclear factor-kappa B (NF-kappa B) and 
      the production of proinflammatory chemokines monocyte chemoattractant protein-1 
      (MCP-1), IL-8, and IFN-inducible protein-10 (IP-10). The exposure of MC to AIgA 
      rapidly activated a NF-kappa B complex constituted of p50 and p65 subunits. 
      NF-kappa B activation was dose dependent, abolished by preincubation with IgA Fc 
      fragments (indicating that AIgA effects occur via specific Fc alpha R), and 
      attenuated by kinase inhibitors. MC stimulation with AIgA increased the mRNA 
      expression of MCP-1, IL-8, and IP-10 in a time- and dose-dependent manner. 
      Maximal expression of IL-8 was observed at 3 h (4.5-fold), while IP-10 and MCP-1 
      peaked at 6 h (5-fold for both). AIgA also induced biosynthesis and release of 
      the chemokines, which presented biological activity in neutrophil and monocyte 
      chemoattractant assays, peaking at 6 and 9 h, respectively. MC pretreatment with 
      the antioxidant pyrrolidine dithiocarbamate inhibited NF-kappa B activation and 
      chemokine mRNA expression. This study shows that stimulation of Fc alphaR in MC 
      induces gene expression of MCP-1, IL-8, and IP-10, a process partially mediated 
      by NF-kappa B activation. These data may be of importance for a better 
      understanding of the pathogenesis of glomerular damage in IgA immune 
      complex-related diseases.
FAU - Duque, N
AU  - Duque N
AD  - Renal Research Laboratory, Jimenez Diaz Foundation, Autonoma University, Madrid, 
      Spain.
FAU - Gomez-Guerrero, C
AU  - Gomez-Guerrero C
FAU - Egido, J
AU  - Egido J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Chemokines)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Fc(alpha) receptor)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Fc)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigens, CD/*metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Chemokine CXCL10
MH  - Chemokines/*biosynthesis/genetics
MH  - *Chemokines, CXC
MH  - Gene Expression Regulation/drug effects/immunology
MH  - Glomerular Mesangium/cytology/*immunology/metabolism
MH  - Humans
MH  - Immunoglobulin A/*metabolism/pharmacology
MH  - *Interferon-gamma
MH  - Interleukin-8/*biosynthesis/genetics
MH  - NF-kappa B/*metabolism/pharmacology
MH  - Receptors, Fc/*metabolism
MH  - Solubility
MH  - Transcription, Genetic/drug effects/immunology
MH  - Transcriptional Activation/immunology
EDAT- 1997/10/08 00:00
MHDA- 1997/10/08 00:01
CRDT- 1997/10/08 00:00
PHST- 1997/10/08 00:00 [pubmed]
PHST- 1997/10/08 00:01 [medline]
PHST- 1997/10/08 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1997 Oct 1;159(7):3474-82.