PMID- 23583823
OWN - NLM
STAT- MEDLINE
DCOM- 20140722
LR  - 20131209
IS  - 1569-1802 (Electronic)
IS  - 0945-053X (Linking)
VI  - 32
IP  - 7-8
DP  - 2013 Oct-Nov
TI  - Combined effects of interleukin-1alpha and transforming growth factor-beta1 on 
      modulation of human cardiac fibroblast function.
PG  - 399-406
LID - S0945-053X(13)00065-6 [pii]
LID - 10.1016/j.matbio.2013.03.008 [doi]
AB  - During cardiac remodeling, cardiac fibroblasts (CF) are influenced by increased 
      levels of interleukin-1alpha (IL-1alpha) and transforming growth factor-beta1 (TGFbeta1). The 
      present study investigated the interaction between these two important cytokines 
      on function of human CF and their differentiation to myofibroblasts (CMF). CF 
      were isolated from human atrial appendage and exposed to IL-1alpha and/or TGFbeta1 (both 
      0.1 ng/ml). mRNA expression levels of selected genes were determined after 6-24h 
      by real-time RT-PCR, while protein levels were analyzed at 24-48 h by ELISA or 
      western blot. Activation of canonical signaling pathways (NFkappaB, Smad3, p38 MAPK) 
      was determined by western blotting. Differentiation to CMF was examined by 
      collagen gel contraction assays. Exposure of CF to IL-1alpha alone enhanced levels of 
      IL-6, IL-8, matrix metalloproteinase-3 (MMP3) and collagen III (COL3A1), but 
      reduced the CMF markers alpha-smooth muscle actin (alphaSMA) and connective tissue growth 
      factor (CTGF/CCN2). By contrast, TGFbeta1 alone had minor effects on IL-6, IL-8 and 
      MMP3 levels, but significantly increased levels of the CMF markers alphaSMA, CTGF, 
      COL1A1 and COL3A1. Co-stimulation with both IL-1alpha and TGFbeta1 increased MMP3 
      expression synergistically. Furthermore, while TGFbeta1 had no effect on 
      IL-1alpha-induced IL-6 or IL-8 levels, co-stimulation inhibited the TGFbeta1-induced 
      increase in alphaSMA and blocked the gel contraction caused by TGFbeta1. Combining IL-1alpha 
      and TGFbeta1 had no apparent effect on their canonical signaling pathways. In 
      conclusion, IL-1alpha and TGFbeta1 act synergistically to stimulate MMP3 expression in 
      CF. Moreover, IL-1alpha has a dominant inhibitory effect on the phenotypic switch of 
      CF to CMF induced by TGFbeta1.
CI  - Copyright (c) 2013 International Society of Matrix Biology. Published by Elsevier 
      B.V. All rights reserved.
FAU - van Nieuwenhoven, Frans A
AU  - van Nieuwenhoven FA
AD  - Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), 
      Maastricht University, Maastricht, The Netherlands. Electronic address: 
      f.vannieuwenhoven@maastrichtuniversity.nl.
FAU - Hemmings, Karen E
AU  - Hemmings KE
FAU - Porter, Karen E
AU  - Porter KE
FAU - Turner, Neil A
AU  - Turner NA
LA  - eng
PT  - Journal Article
DEP - 20130412
PL  - Netherlands
TA  - Matrix Biol
JT  - Matrix biology : journal of the International Society for Matrix Biology
JID - 9432592
RN  - 0 (COL3A1 protein, human)
RN  - 0 (Collagen Type III)
RN  - 0 (Interleukin-1alpha)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Blotting, Western
MH  - Collagen Type III/metabolism
MH  - Fibroblasts/metabolism/*physiology
MH  - Gene Expression Regulation/*genetics
MH  - Humans
MH  - Interleukin-1alpha/genetics/*metabolism
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Myocardium/*cytology/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*physiology
MH  - Transforming Growth Factor beta1/genetics/*metabolism
OTO - NOTNLM
OT  - CF
OT  - CMF
OT  - COL1A1
OT  - COL3A1
OT  - CTGF
OT  - Cardiac fibroblasts
OT  - Cytokines
OT  - ECM
OT  - Extracellular matrix
OT  - Fibrosis
OT  - IL
OT  - Inflammation
OT  - MMP
OT  - Remodeling
OT  - TGFbeta1
OT  - TNFalpha
OT  - alpha-smooth muscle actin
OT  - cardiac fibroblast
OT  - cardiac myofibroblast
OT  - collagen I
OT  - collagen III
OT  - connective tissue growth factor
OT  - extracellular matrix
OT  - interleukin
OT  - matrix metalloproteinase
OT  - transforming growth factor beta1
OT  - tumor necrosis factor alpha
OT  - alphaSMA
EDAT- 2013/04/16 06:00
MHDA- 2014/07/23 06:00
CRDT- 2013/04/16 06:00
PHST- 2013/02/11 00:00 [received]
PHST- 2013/03/27 00:00 [revised]
PHST- 2013/03/27 00:00 [accepted]
PHST- 2013/04/16 06:00 [entrez]
PHST- 2013/04/16 06:00 [pubmed]
PHST- 2014/07/23 06:00 [medline]
AID - S0945-053X(13)00065-6 [pii]
AID - 10.1016/j.matbio.2013.03.008 [doi]
PST - ppublish
SO  - Matrix Biol. 2013 Oct-Nov;32(7-8):399-406. doi: 10.1016/j.matbio.2013.03.008. 
      Epub 2013 Apr 12.