PMID- 18751966
OWN - NLM
STAT- MEDLINE
DCOM- 20081118
LR  - 20220223
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 51
IP  - 11
DP  - 2008 Nov
TI  - Effects of different LDL particles on inflammatory molecules in human mesangial 
      cells.
PG  - 2117-25
LID - 10.1007/s00125-008-1127-4 [doi]
AB  - AIMS/HYPOTHESIS: Inflammation is a mechanism of glomerular damage in chronic 
      glomerulopathies. LDL may increase the production of inflammatory cytokines in 
      renal tissues. However, the relative role of native, oxidised and glycated LDL in 
      promoting this process has been only partially elucidated. METHODS: We tested the 
      inflammatory and proapoptotic effects of native, oxidised and glycated LDL in 
      human mesangial cells (HMCs) by measuring levels of IL6, CD40 and macrophage 
      migration inhibitory factor (MIF) genes, MIF protein, release of IL6, soluble 
      CD40, fibronectin and laminin, early and late apoptosis, and extracellular 
      regulated kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK) activation. 
      RESULTS: IL6 and CD40 mRNA were dose-dependently upregulated by all three 
      species; this was closely paralleled by their increased release. MIF mRNA was 
      potently stimulated by modified LDL, as confirmed by immunostaining. Fibronectin 
      and laminin release was stimulated by both oxidised and glycated, but not native, 
      LDL. All LDL species induced some increase in late, but not early, apoptosis, and 
      similarly activated JNK2/3 phosphorylation; in contrast, ERK1/2 phosphorylation 
      was more strongly upregulated by oxidised than either native or glycated LDL. 
      CONCLUSIONS: In HMCs, the production and release of IL6 and CD40 is stimulated by 
      both native and modified LDL, while MIF is more strongly stimulated by oxidised 
      LDL. Regarding the pattern of mesangial expansion, fibronectin and laminin are 
      upregulated by oxidised and glycated LDL. Apoptosis, if modest, is induced by all 
      species. Intracellular signalling of native and modified LDL involves JNK2/3 and, 
      perhaps more specifically, ERK1/2. Tight control of the lipid profile may be 
      useful in preserving kidney function in patients with metabolic alterations.
FAU - Santini, E
AU  - Santini E
AD  - Department of Internal Medicine, University of Pisa, Via Roma 67, I-56100, Pisa, 
      Italy.
FAU - Lupi, R
AU  - Lupi R
FAU - Baldi, S
AU  - Baldi S
FAU - Madec, S
AU  - Madec S
FAU - Chimenti, D
AU  - Chimenti D
FAU - Ferrannini, E
AU  - Ferrannini E
FAU - Solini, A
AU  - Solini A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080828
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Antigens, CD)
RN  - 0 (CD40 Antigens)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (RNA, Messenger)
RN  - 0 (glycated lipoproteins, LDL)
RN  - 0 (oxidized low density lipoprotein)
SB  - IM
MH  - Antigens, CD/genetics
MH  - CD40 Antigens/genetics
MH  - Glomerular Mesangium/drug effects/*physiopathology
MH  - Glycation End Products, Advanced
MH  - Humans
MH  - Inflammation/*physiopathology
MH  - Interleukin-6/genetics
MH  - Lipoproteins, LDL/blood/isolation & purification/*pharmacology
MH  - RNA, Messenger/drug effects/genetics
EDAT- 2008/08/30 09:00
MHDA- 2008/11/19 09:00
CRDT- 2008/08/30 09:00
PHST- 2008/05/03 00:00 [received]
PHST- 2008/07/15 00:00 [accepted]
PHST- 2008/08/30 09:00 [pubmed]
PHST- 2008/11/19 09:00 [medline]
PHST- 2008/08/30 09:00 [entrez]
AID - 10.1007/s00125-008-1127-4 [doi]
PST - ppublish
SO  - Diabetologia. 2008 Nov;51(11):2117-25. doi: 10.1007/s00125-008-1127-4. Epub 2008 
      Aug 28.