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Induction of UVB-induced apoptotic cell in keratinocytes and its pathological homology with sunburn cell
JSID Abstracts/J. Dermatol. Sci. 8 (1994) 54-88
60
031
034
EFFECT OF A VITAMIN C18ANALOGUE ON THE GROWTH, DIFFERENTIATION, CELL CYCLE, AND RETINOBLASTWA CULTURED NORMAL HUMAN KERATINOCYTES T. KOSAYASHI’. Dermatology.
K. HASHIMOTO
and K. YOSHIKAWA,
Osaka University School of Medii~~
PROTEIN
‘Department
SUPPRESSION OF SECRETORY COMPONENT EXPRESSION IN CULTURED KERATINGCYTES BY PSORIASIS-INDUCIBLE DRUGS. Y. NIHEI and F. KANEKO. Department of Domratology. Fukushima
OF
of
Medical College, Fukushima, Japan.
Suita, Osaka, Japan
Recently, some agents are reported to be related in the pathogenesis of psoriasis or provocation of psoriatic lesions. We have already reported that secretory component (SC) which is produced by keratinocytes works as an inhibitor of gamma-interferon (EN-y).
ST232 is one of vitamin D, ana!-ogue. which is explored as a new therapeutic agent of psoriasis. We presented that ST232 induced the growlh inhibition and dbrentialion of cultured normal human keratinocyies more effectiveiy than 1,25(OH),D,. me relinoblastoma protein (pRB), one of tumw suppressor, is involved In the growth reguhtion of normal cells, namely cell cyole regulation. It undergoes cell-cyole-dependent phosphorylation and daphos#orylation. The underphosphoryiated form of pRb regulates the transfer from Gl to S phase. To elucidate the meohanlsm of ST2324nducad growlh inhibiiion, WB analyzed oell cyole dist&utiin and the alteration of hyperphosphorylaled and underphosphorylaled state of pRB in human keralinocytes treated with ST232. ST232 induoed orowth anest in Gl/GO and G2+M and the increase of the underphospho$aied form of pRB in human karatinocytes.
In this report, we studied whether psoriasis-inducible drugs affect on SC expression in culhlred keratinccytea by ELlSA and flowcytometry. Results: Propranolol and carteolol (beta-blockers), captopril (angiotensin converting enzyme inhibitor) and diltiazem (calcium antagonist) showed suppressive effects on SC expression in cultured
keratinocytes except for hichlormethiazide and furcsemide (diuretics). Propranolol also prolongated ICAM- I expression on keratinocytea induced by 1FN-y as an early step of infIammatory process. The suppression of SC expression by the drugs may explain a part of the mechanism of drug-induced psoriasis.
032
035
Cyclosporin human
A inhibits
keratinocytes
H. KATAYAMA.
and
K. USUI
cyclosporin
A
Effects
of
Primary
cultured
plates were treated 5, 1.. 0.1 B g/ml)
After fixation. IFN 7, ICAMonly the
et
only
upregulated rate
17237%).
ession
partly
keratinocytes
at
vein
endothelial
Department
(CyA)
on
human
keratinocytes
adhesion
treated with
cells. of Dermatology.
molecule,
ICAM-I.
in confluency
with
CyA
inhibited
10 B g/ml
the
inhibited
The
results
by
inhibiting
and vascular
rh.
(lo-,
IL-1 a
5-,
I-,
were (lo-. cells
(lOOng/ml)
0.1
upregulstion
IL-1 (I upregulated
it 2.0-2.5fold.
K. MARUYAMA. JZ. ZHANG, K. IWATSUKI, 1. ON0 and F. KANEKO. Department of Dermatology, Fukushima Medical College. Fukushima. Japan
in 9G-well
ji g/ml)
or rh. for
subjected to cell-ELISA. Upon stimulation of karatinocytes increased 1.5-2.5 fold.
5 p g/ml
REGULATORY EFFECTS OF GAMMA-INTERFERON (IFN-y) ON INTERLEUKIN-8 (IL-E) SECRETION BY CULTURED HUMAN KERATINOCYTES AND DERMAL FIBROBLASTS
of cultured
Japan
were
together
24-94%).
umbilical
expression
rh. IFN 7 (500 U/ml) together with CyA 42.h. Human umbilical vein endothelial
they were expression
IO- and
former,
d. CyA
with for
in confluency (lOOng/ml)
ICAM-
and H. YAOITA,
Tochigi,
studied.
TNFa
human
School,
Jichi Medical
(HUVEC)
cytokine-induced
ICAM-
it (inhibition
CyA
only
may
at IO B g/ml
indicate
that
cytokine-induced endothelial
(inhibition of HUVEC
CyA
rate,
ceuses ICAM-I
rate
by
2.0-2.5-f&
35-4496).
inhibited
4h. with CyA
TNF
n
it (inhibition immunosupprexpression
of
cells.
secretion
by
various
cells
in
a
different
manner.
036
033 HLA-DPBI’OB ALLELE AND IN THE HLA-DNA ANALYSIS
IFNq released by T cells might affect other cytokines in inflamed skin lesions. To clarify the effects of IFN-7 on IL-8 secretion, normal human keratinocytes (NHKs) , a squamous cell carcinoma cell line (HSC-1) cells and dermal fibroblasts (HDFs) were incubated with IFN-1 (100 IU/ml) in the presence of various stimulants. IL-8 spontaneously secreled by NHKs was about O.lng/IO~cells. which was lower than HSC-I cells (5ng/l05cells). and IL-8 by NHKs increased more than 20 times by PMA (IOnM) stimulation. IFN-Y suppressed IL-8 secretion by both HSC-1 cells and PMA-slimulaled NHKs. although IL-8 secrelion from NHKs slimulated with or without IL-la and TNFa wss accelerated by IFN-7. On the other hand, IFN-1 showed inhibitory effects on IL-8 secrelion by HDFs. These results suggesl tbal IFN-y regulates IL-8
SUSCEPTIBILITY
TO
GENERALIZED PUSTULAR PSORIASIS
CULTURE CONDITION OF WAN KERATINOWlW NHICSSHlWSTGESAME CQPOSITIONSOF FATTYACIDAS THOSEIN F’SORIASIS VDIGARIS
Ohkidol
N. Niyaharcl. A. Ozrwl. J. Surei’. M. , T. Neruas2. H. Inok@, ‘Dspartesnt of Orrmatolcgy end eGsnstic H. KcbeyeshP and A. OhkwerasI Information, Division of Ncleculer Life Science, Tckai University School. of Medicine. Irehere. Kane~wa end 30eperteent of Dereetclcgy. Hckkaidc University School of Nedicins. Swpcrc. Hckkaidc. Japan HLA-DNA typing of HLA class II antigens wae performed in generalized pustclar psoriasis (GPP) to investigate the pathcgsnesir in the disease. SUBJECTS:Nine patients with GPP were anrlized. As the controls. the data of 307 Japanese healthy controls in the 11th International Histcccmpatibi I ity Wcrkrhcp. 1991 were refsred. METHODS:HLA-DNA typing for HLA class II antigens (HLA-ORBI’, DPAI’.DOBl’ and OpBl’) using the PCR-RFLP nsthcd we carried cut. RESULTS:Eight of 9 patients with CPP had ens or two alleles of the HLADPBl’O3(WB1’0301, DQBl’O302 and DPB1’03LN) (rr=13.41. x2=11 .24. p
if. NAGAI. Y. tIAHAMT0. tL FDRlMoTO, IL SDlU, C. ASAGAM Department of Dernrtology, Yamguchi Oniversity, Ubs City. Japan Linoleic
acid
is important
for biological
function
of epidermis.
In the condition of linoleic acid deficiency, epidermis contain much are oleic acid in stead of linoleic acid. Psoriatic scales also have mch aore oleic acid with the But the increase of oleic acid in decrease of linoleic acid. psoriatic scales is greater than that in non-psoriatic scales. although the levels of linoleic acid in both aaterials losered to tha saae degree. That is a characteristic feature of fatty acid commsitions in psoriatic scales. In this study, we analysed fatty acid compositions of cultured human keratinocytes in various conditions to find the specific condition that leads to much increase of oleic acid in keratinocytes.
60
031
034
EFFECT OF A VITAMIN C18ANALOGUE ON THE GROWTH, DIFFERENTIATION, CELL CYCLE, AND RETINOBLASTWA CULTURED NORMAL HUMAN KERATINOCYTES T. KOSAYASHI’. Dermatology.
K. HASHIMOTO
and K. YOSHIKAWA,
Osaka University School of Medii~~
PROTEIN
‘Department
SUPPRESSION OF SECRETORY COMPONENT EXPRESSION IN CULTURED KERATINGCYTES BY PSORIASIS-INDUCIBLE DRUGS. Y. NIHEI and F. KANEKO. Department of Domratology. Fukushima
OF
of
Medical College, Fukushima, Japan.
Suita, Osaka, Japan
Recently, some agents are reported to be related in the pathogenesis of psoriasis or provocation of psoriatic lesions. We have already reported that secretory component (SC) which is produced by keratinocytes works as an inhibitor of gamma-interferon (EN-y).
ST232 is one of vitamin D, ana!-ogue. which is explored as a new therapeutic agent of psoriasis. We presented that ST232 induced the growlh inhibition and dbrentialion of cultured normal human keratinocyies more effectiveiy than 1,25(OH),D,. me relinoblastoma protein (pRB), one of tumw suppressor, is involved In the growth reguhtion of normal cells, namely cell cyole regulation. It undergoes cell-cyole-dependent phosphorylation and daphos#orylation. The underphosphoryiated form of pRb regulates the transfer from Gl to S phase. To elucidate the meohanlsm of ST2324nducad growlh inhibiiion, WB analyzed oell cyole dist&utiin and the alteration of hyperphosphorylaled and underphosphorylaled state of pRB in human keralinocytes treated with ST232. ST232 induoed orowth anest in Gl/GO and G2+M and the increase of the underphospho$aied form of pRB in human karatinocytes.
In this report, we studied whether psoriasis-inducible drugs affect on SC expression in culhlred keratinccytea by ELlSA and flowcytometry. Results: Propranolol and carteolol (beta-blockers), captopril (angiotensin converting enzyme inhibitor) and diltiazem (calcium antagonist) showed suppressive effects on SC expression in cultured
keratinocytes except for hichlormethiazide and furcsemide (diuretics). Propranolol also prolongated ICAM- I expression on keratinocytea induced by 1FN-y as an early step of infIammatory process. The suppression of SC expression by the drugs may explain a part of the mechanism of drug-induced psoriasis.
032
035
Cyclosporin human
A inhibits
keratinocytes
H. KATAYAMA.
and
K. USUI
cyclosporin
A
Effects
of
Primary
cultured
plates were treated 5, 1.. 0.1 B g/ml)
After fixation. IFN 7, ICAMonly the
et
only
upregulated rate
17237%).
ession
partly
keratinocytes
at
vein
endothelial
Department
(CyA)
on
human
keratinocytes
adhesion
treated with
cells. of Dermatology.
molecule,
ICAM-I.
in confluency
with
CyA
inhibited
10 B g/ml
the
inhibited
The
results
by
inhibiting
and vascular
rh.
(lo-,
IL-1 a
5-,
I-,
were (lo-. cells
(lOOng/ml)
0.1
upregulstion
IL-1 (I upregulated
it 2.0-2.5fold.
K. MARUYAMA. JZ. ZHANG, K. IWATSUKI, 1. ON0 and F. KANEKO. Department of Dermatology, Fukushima Medical College. Fukushima. Japan
in 9G-well
ji g/ml)
or rh. for
subjected to cell-ELISA. Upon stimulation of karatinocytes increased 1.5-2.5 fold.
5 p g/ml
REGULATORY EFFECTS OF GAMMA-INTERFERON (IFN-y) ON INTERLEUKIN-8 (IL-E) SECRETION BY CULTURED HUMAN KERATINOCYTES AND DERMAL FIBROBLASTS
of cultured
Japan
were
together
24-94%).
umbilical
expression
rh. IFN 7 (500 U/ml) together with CyA 42.h. Human umbilical vein endothelial
they were expression
IO- and
former,
d. CyA
with for
in confluency (lOOng/ml)
ICAM-
and H. YAOITA,
Tochigi,
studied.
TNFa
human
School,
Jichi Medical
(HUVEC)
cytokine-induced
ICAM-
it (inhibition
CyA
only
may
at IO B g/ml
indicate
that
cytokine-induced endothelial
(inhibition of HUVEC
CyA
rate,
ceuses ICAM-I
rate
by
2.0-2.5-f&
35-4496).
inhibited
4h. with CyA
TNF
n
it (inhibition immunosupprexpression
of
cells.
secretion
by
various
cells
in
a
different
manner.
036
033 HLA-DPBI’OB ALLELE AND IN THE HLA-DNA ANALYSIS
IFNq released by T cells might affect other cytokines in inflamed skin lesions. To clarify the effects of IFN-7 on IL-8 secretion, normal human keratinocytes (NHKs) , a squamous cell carcinoma cell line (HSC-1) cells and dermal fibroblasts (HDFs) were incubated with IFN-1 (100 IU/ml) in the presence of various stimulants. IL-8 spontaneously secreled by NHKs was about O.lng/IO~cells. which was lower than HSC-I cells (5ng/l05cells). and IL-8 by NHKs increased more than 20 times by PMA (IOnM) stimulation. IFN-Y suppressed IL-8 secretion by both HSC-1 cells and PMA-slimulaled NHKs. although IL-8 secrelion from NHKs slimulated with or without IL-la and TNFa wss accelerated by IFN-7. On the other hand, IFN-1 showed inhibitory effects on IL-8 secrelion by HDFs. These results suggesl tbal IFN-y regulates IL-8
SUSCEPTIBILITY
TO
GENERALIZED PUSTULAR PSORIASIS
CULTURE CONDITION OF WAN KERATINOWlW NHICSSHlWSTGESAME CQPOSITIONSOF FATTYACIDAS THOSEIN F’SORIASIS VDIGARIS
Ohkidol
N. Niyaharcl. A. Ozrwl. J. Surei’. M. , T. Neruas2. H. Inok@, ‘Dspartesnt of Orrmatolcgy end eGsnstic H. KcbeyeshP and A. OhkwerasI Information, Division of Ncleculer Life Science, Tckai University School. of Medicine. Irehere. Kane~wa end 30eperteent of Dereetclcgy. Hckkaidc University School of Nedicins. Swpcrc. Hckkaidc. Japan HLA-DNA typing of HLA class II antigens wae performed in generalized pustclar psoriasis (GPP) to investigate the pathcgsnesir in the disease. SUBJECTS:Nine patients with GPP were anrlized. As the controls. the data of 307 Japanese healthy controls in the 11th International Histcccmpatibi I ity Wcrkrhcp. 1991 were refsred. METHODS:HLA-DNA typing for HLA class II antigens (HLA-ORBI’, DPAI’.DOBl’ and OpBl’) using the PCR-RFLP nsthcd we carried cut. RESULTS:Eight of 9 patients with CPP had ens or two alleles of the HLADPBl’O3(WB1’0301, DQBl’O302 and DPB1’03LN) (rr=13.41. x2=11 .24. p
if. NAGAI. Y. tIAHAMT0. tL FDRlMoTO, IL SDlU, C. ASAGAM Department of Dernrtology, Yamguchi Oniversity, Ubs City. Japan Linoleic
acid
is important
for biological
function
of epidermis.
In the condition of linoleic acid deficiency, epidermis contain much are oleic acid in stead of linoleic acid. Psoriatic scales also have mch aore oleic acid with the But the increase of oleic acid in decrease of linoleic acid. psoriatic scales is greater than that in non-psoriatic scales. although the levels of linoleic acid in both aaterials losered to tha saae degree. That is a characteristic feature of fatty acid commsitions in psoriatic scales. In this study, we analysed fatty acid compositions of cultured human keratinocytes in various conditions to find the specific condition that leads to much increase of oleic acid in keratinocytes.