PMID- 17960400
OWN - NLM
STAT- MEDLINE
DCOM- 20080424
LR  - 20181201
IS  - 0340-3696 (Print)
IS  - 0340-3696 (Linking)
VI  - 300
IP  - 1
DP  - 2008 Jan
TI  - The role of heparin-binding EGF-like growth factor and amphiregulin in the 
      epidermal proliferation of psoriasis in cooperation with TNFalpha.
PG  - 37-45
AB  - Heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin (AREG) are the 
      members of EGF family that bind to common EGF receptor (EGFR) in the epidermis. 
      However, the role of these two growth factors in epidermal hyperplasia of 
      psoriasis has not been established. On the other hand, CD4+ T cells are 
      responsible for the development of the psoriatic plaques. However, inflammatory 
      cytokines, such as TNFalpha, IL-1beta and IFNgamma, inhibit the growth of human 
      keratinocytes in vitro. The expression of HB-EGF, AREG and EGFR proteins in 
      normal (n = 22) and psoriatic (n = 34) skin tissues was examined by 
      immunohistochemistry. Then, the effects of HB-EGF and AREG on the growth of 
      cultured adult normal human epidermal keratinocytes (NHEK-AD) with or without TH1 
      cytokines, such as TNFalpha, IL-1beta and IFNgamma, were examined by 
      3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, and 
      the effects of these cytokines on the expression of EGFR mRNA in NHEK-AD were 
      examined by real-time reverse transcriptase-polymerase chain reaction. The 
      expression of HB-EGF and AREG in the epidermis was not specific to psoriatic 
      plaques, but the distribution of positive cells throughout the epidermis was 
      different between normal skins and psoriatic plaques. On the other hand, in the 
      dermis and the papillary dermis, most of vascular endothelial cells and 
      infiltrating mononuclear cells expressed both HB-EGF and AREG in normal skins and 
      psoriatic plaques, and these positive cells were more frequent in psoriasis 
      compared to normal skin. In the in vitro growth assay, HB-EGF, not AREG, 
      stimulated the proliferation of NHEK-AD at the optimal concentration of 1 ng/ml. 
      Furthermore, HB-EGF compensated the growth-suppressing effects of TNFalpha, 
      IL-1beta and IFNgamma on NHEK-AD, and TNFalpha promoted the growth of NHEK-AD at 
      the concentration of 2 and 20 U/ml in combination with HB-EGF and, in lesser 
      extent, with AREG. However, TNFalpha did not affect the expression of EGFR mRNA 
      in NHEK-AD. Growth factors and inflammatory cytokines produced in the dermis 
      would be important for the epidermal proliferation in psoriatic plaques and 
      TNFalpha may play a key role in cooperation with HB-EGF and AREG in the 
      proliferation of epidermal keratinocytes at the psoriatic skin lesions.
FAU - Yoshida, Aki
AU  - Yoshida A
AD  - Department of Pathology, Iwate Medical University School of Medicine, 19-1 
      Uchimaru, Morioka 020-8505, Japan.
FAU - Kanno, Hiroyuki
AU  - Kanno H
FAU - Watabe, Daisuke
AU  - Watabe D
FAU - Akasaka, Toshihide
AU  - Akasaka T
FAU - Sawai, Takashi
AU  - Sawai T
LA  - eng
PT  - Journal Article
DEP - 20071025
PL  - Germany
TA  - Arch Dermatol Res
JT  - Archives of dermatological research
JID - 8000462
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (HBEGF protein, human)
RN  - 0 (Heparin-binding EGF-like Growth Factor)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-1beta)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Amphiregulin
MH  - Case-Control Studies
MH  - *Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - EGF Family of Proteins
MH  - Epidermis/drug effects/*metabolism/*pathology
MH  - ErbB Receptors/metabolism
MH  - Glycoproteins/*metabolism/pharmacology
MH  - Heparin-binding EGF-like Growth Factor
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism/pharmacology
MH  - Interferon-gamma/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Keratinocytes/metabolism/pathology
MH  - Middle Aged
MH  - Psoriasis/*metabolism/pathology
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
EDAT- 2007/10/26 09:00
MHDA- 2008/04/25 09:00
CRDT- 2007/10/26 09:00
PHST- 2007/05/30 00:00 [received]
PHST- 2007/10/08 00:00 [accepted]
PHST- 2007/09/13 00:00 [revised]
PHST- 2007/10/26 09:00 [pubmed]
PHST- 2008/04/25 09:00 [medline]
PHST- 2007/10/26 09:00 [entrez]
AID - 10.1007/s00403-007-0809-y [doi]
PST - ppublish
SO  - Arch Dermatol Res. 2008 Jan;300(1):37-45. doi: 10.1007/s00403-007-0809-y. Epub 
      2007 Oct 25.