PMID- 17572012
OWN - NLM
STAT- MEDLINE
DCOM- 20070907
LR  - 20111117
IS  - 1079-9907 (Print)
IS  - 1079-9907 (Linking)
VI  - 27
IP  - 6
DP  - 2007 Jun
TI  - Native human IFN-alpha is a more potent suppressor of HDF response to profibrotic 
      stimuli than recombinant human IFN-alpha.
PG  - 481-90
AB  - Interferon-alpha(IFN-alpha) inhibits fibroblast proliferation, differentiation 
      into myofibroblasts, and extracellular matrix synthesis, which are key events 
      during both normal wound repair and fibrotic lesion formation. Unlike recombinant 
      human IFN-alpha (rHuIFN-alpha), a native human IFN-alpha (nHuIFN-alpha) consists 
      of several IFN-alpha subtypes and traces of other cytokines produced by the 
      Sendai virus-stimulated human leukocytes. This study compares the antifibrotic 
      effect of nHuIFN-alpha and rHuIFN-alpha in normal human dermal fibroblasts 
      (HDFs). Treatment of HDF culture with nHuIFNA-alpha markedly affects HDF 
      viability, whereas different rHuIFN-alpha subtypes show various effects. Two of 
      twelve rHuIFN-alpha subtypes (IFN-alpha B2 and IFN-alpha K) significantly reduce 
      cell viability of HDFs compared with nontreated HDFs. However, nHuIFN-alpha 
      significantly reduces HDF cell viability in comparison to both nontreated cells 
      and cells treated with rHuIFN-alpha. The 50% inhibitory concentration (IC(50)) 
      varied 10-fold between nHuIFN-alpha and rHuIFN-alpha (1,103 IU/mL and 10,762 
      IU/mL, respectively). The impact on procollagen type I mRNA synthesis level is 
      comparable at low doses of IFN (100 and 500 IU/mL), whereas at the dose of 1,000 
      IU/mL, nHuIFN-alpha shows higher repression of collagen type I gene than does 
      rHuIFN-alpha. Both, nHuIFN-alpha and rHuIFN-alpha antagonize the effect of 
      exogenous transforming growth factor-beta (TGF-beta) and interleukin-4 (IL-4) as 
      measured by the alpha-smooth muscle actin (alpha -SMA) and procollagen type I 
      mRNA level, but the effect of nHuIFN-alpha is more pronounced. This study 
      suggests that nHuIFN-alpha is a more potent suppressor of the HDF response to 
      profibrotic stimuli than rHuIFN-alpha, probably because of the synergism between 
      different IFN-alpha subtypes and antifibrotic cytokines and factors.
FAU - Santak, Goran
AU  - Santak G
AD  - General County Hospital, Pozega, Croatia.
FAU - Santak, Maja
AU  - Santak M
FAU - Forcic, Dubravko
AU  - Forcic D
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (Actins)
RN  - 0 (Collagen Type I)
RN  - 0 (Interferon Type I)
RN  - 0 (Interferon-alpha)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Actins/genetics
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Collagen Type I/genetics
MH  - Fibroblasts
MH  - Gene Expression Regulation
MH  - Humans
MH  - Interferon Type I/genetics/metabolism/pharmacology
MH  - Interferon-alpha/genetics/*metabolism/*pharmacology
MH  - Interleukin-4/antagonists & inhibitors
MH  - RNA, Messenger/genetics
MH  - Recombinant Proteins
MH  - Skin/cytology/*drug effects/metabolism
MH  - Transforming Growth Factor beta/antagonists & inhibitors
EDAT- 2007/06/19 09:00
MHDA- 2007/09/08 09:00
CRDT- 2007/06/19 09:00
PHST- 2007/06/19 09:00 [pubmed]
PHST- 2007/09/08 09:00 [medline]
PHST- 2007/06/19 09:00 [entrez]
AID - 10.1089/jir.2007.0174 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 2007 Jun;27(6):481-90. doi: 10.1089/jir.2007.0174.