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009 The effects of interferons on interleukin(IL)-6 and IL-8 production from human keratinocytes
JSID
104
007
010
EXPRESSION OF IL-1 S BY HUMAN SQUAMOUS CARCINOMA CELL LINE CELLS IS UP-REGULATED BY IFN- T AND INHIBITED BY ‘t -Hsn.uki lnoua, e Department of Dermatology, Fukushima Medical College, Fukushima, Japan IL-1 5 is a newly described cytokine that shares many biologlcal activities with IL-Z. Previous studies demonstrated that keratinocytes express IL-1 F which might be involved in T cell-mediated cutaneous diseases. We screened the expression of Y-15 jn varjnus cell types by RT-PCR, and further investigated the affects of IFN- T, cyclosporin A (CsA), and dexamethasone on IL-1 5 expression by human squamous carcinoma cell line (HSC) cells, using northern hybridization. High doses of IFN-r increased the expression of IL-1 S by HSC. whereas
dexatnethaaona completely Inhibited the expression at a concentration
of
10.6 M. In contrast, CsA has no affect on the expression at a concentration of 1 rrg/ml. These findings suggest that anti-inflammatory effects of
dexamethaaone IL-l 5.
may partly ba caused by inhlbltlon of keratinocyte-derived
008
INDUCTION Oil INTERLEUKIN 1 RECEPTOR ANTAGONIST IN KERATINOCYTES BY INFLAMMATORY CYTOKINES. T. Aokl. Institute for Advanced Skin Research Inc./Shiseido Center, Yokohama, Japan. We have previously repofied that content of IL-1 receptor antagonist (IL-lra) is markedly elevated in the stratum comeum of sun-exposed arca, UV-irradiated arca, and various inflammatory skin disorders. The purpose of this study is to examine the involvement of inflammatory cytokines on induction of an anti-inflammatory cytokine, IL-In+, in keratinocytes. Human keratinocytes, which were cultivated in the presence of mitomycin C-treated 333-12 feeder layer, were tteated with various cytokines, including IL-la, 8, TNF-a. TGF-a. 8, and IFN-I. Contents of IL-lra in kemdnocytes were examined by Western blotting or ELISA. IL-lra expression was enhanced markedly by IFN-1, and moderately by IL- la, 8, and TNF-a, but not by TGF-a and p. These results suggest that inflammatory cpokines produced by keratinocytes or infiltrating leukocytes can induce IL-lra in keratinocytes. Induction of IL-ha in kemtinocytes by inflammatory cytokincs may rcflcct a homeostalic response of the skin against various stimuli.
011
INTERLBUKIN (IL)-la AND INTERFERON-y INDUCE TUMOR NECROSIS FACTOR Oa PRODUCTION FROM HUMAN KERATINOCY’I’BS K. ~atsu~m. H. Fujlsawa, F. Otsuka. Dcpartmcnt of Dermatology, University of Tsukuba, Tsukuba, Japan. Tumor necrosis factor-a (TNF-a) is a proinflammatory cytokine and known to be produced by a wide variety of ceils including human keratinocytea (KCs). Altough ultraviolet B and lipopolysaccharlde are known to induce TNF-a production from human KCs, what types of cytokines induce TNF-a production was unclear. In the pnsent study, we have demonstrated that lntcrleukin (IL)-la and interferon (lFN)- y induced TNF-a, but no induction of TNF-a was observed with either IFN- a or IFN-8. Combined treatment with IL-la and IFNy induced TNF-a production synergistically. These results suggest that IL-la and IFN-y are a positive regulator for the production of TNF-a fmm human KCs and likely has an augmentative effect on skin inflammation.
009
EFFECT
OF AGING AND PHOTOAGING
ON TI-LE PRODUCTION
AND
EXPRESSION OF IL-lo AND IL-1 RECEPTOR ANTAGONIST IN RESPONSE TO SKIN IRRITANTS. l2.H. Sub. NC. Eun. 1.1. You Department of Dermatology, Seoul National Univeristy College of Medicine: Seoul, Korea Skin aging can be separately considered into photoaging and chronological aeinn. In spite of the expectation that there must be large difference in the &on& pattern to ir&nts, there has been no report io investigate skin aging by comparing prcduction and expression of cytokines in response to various stimuli. This study was done to know the change of the production and expression of IL-lo and IL-l receptor antagonist (IL.-h4 according to age groups with the treatment of UVB. TPA and
SLS. Monolayer keratinccyte cultures were performed using the skin from
newborn, young adults and aged volunteers. Production of cytokines by ELISA were generally decreased with the increase of age. IL-lrs production from forearm skin was significantly reduced compared with that from thigh skin. The cytokine production ratio of irritants-treated group to age-matched control group showed the decrease in case of IL-l% according to skin aging. These ratios were sometimes significantly different between forearm and thigh. The results of mRNA expressions by RT-PCR were diverse. These results indicated that the response patterns with skin aging were various according to the kinds of stimuli. They also suggested that photoaged skin and chronologically aged skin are much different in the production and expression of cytokines.
012
THE BFFECN OF INTERFERONS ON INTERLEUKlN(IL)d AND IL-8 PRODUCnON FROM HUMAN KERATINOCYTES. H. Fu’isawa K Matsuura, F. Otsuka. Department of Dermatology, University+rie o suku a,
~ba
Abstracts
Jepm.
have pleiotrophlc effects including the ability Intcrfemns (IFI%) to induce Interleukln (IL)-6 and IL-8 productions in several cell types. IL-6 and IL-8 are proinflammatov cytoklnes and known to be produced by a wide variety of cells including human keratlnocyte-s. In the present study, we sought to examine the effects of JFNs on IL-6 and IL-8 production from human keratinocytes. IFN-1 induced IL-6, and IL-8 production dose-dependently, but no ihducrion of IL-6 or IL-8 was observed with either IF% a or tFN-E. Combined treatment with IFN-y and IL-la Induced 6-7-fold higher levels of IL-6 than ILla alone. Combined tmatment with IFNq and TNF-a induced 1 I-12-fold higher levels than TNFa alone. The same treatments induced 34-fold higher levels of IL-8 in both cases. These. results suggest that IFN-y is a positive regulator for the production of IL-6 and IL-8 from human keratinocytes and likely has an augmentative effect on skin inflammation.
EFFECT OF STEM CELL FACTOR ON MAST CELL SURVIVAL AND CELL PROLIFERATION IN TRANSPLANTED NEUROFIBROMA IN NUDE MICE.T Demitsu. Department of Dermatology, Jichi Medical School, Tocbigi-ken, Japan Stem cell factor (SCF) plays an important role in the mast cell (MC) prolifemtion and development. However, little has been known the role of SCF on fully matured human skin mast cell (HSMC) in vitro and in vivo. We studied the effects of exogenous SCF on HSMCs in transplanted neurotibroma in nude mice and also examined the cell proliferation of the neurofibmma. Small pieces of neumfibroma in a patient with von Recklinghauscn’s disease were transplanted into the subcutis of nude mice. SCF (10 ng,lOOng) was injected around the neurotibroma tissues. MCs in transplanted neurofibmma injected with vehicle showed decreased in number when compared to those in neurofibroma before transplantation. Injection with SCF recovered MC number in neumfibroma tissue up fo the pre-transplantation level. Injection with SCF increased PCNA-positive cells in transplanted neumfibroma. From these findings HSMC is still capable of responding to SCF in vivo and SCF may play some role in increased MC number of cutaneous neumtibroma. In addition the growth of neurotibroma may relate fo the MC number in von Recklingbausen’s disease.
104
007
010
EXPRESSION OF IL-1 S BY HUMAN SQUAMOUS CARCINOMA CELL LINE CELLS IS UP-REGULATED BY IFN- T AND INHIBITED BY ‘t -Hsn.uki lnoua, e Department of Dermatology, Fukushima Medical College, Fukushima, Japan IL-1 5 is a newly described cytokine that shares many biologlcal activities with IL-Z. Previous studies demonstrated that keratinocytes express IL-1 F which might be involved in T cell-mediated cutaneous diseases. We screened the expression of Y-15 jn varjnus cell types by RT-PCR, and further investigated the affects of IFN- T, cyclosporin A (CsA), and dexamethasone on IL-1 5 expression by human squamous carcinoma cell line (HSC) cells, using northern hybridization. High doses of IFN-r increased the expression of IL-1 S by HSC. whereas
dexatnethaaona completely Inhibited the expression at a concentration
of
10.6 M. In contrast, CsA has no affect on the expression at a concentration of 1 rrg/ml. These findings suggest that anti-inflammatory effects of
dexamethaaone IL-l 5.
may partly ba caused by inhlbltlon of keratinocyte-derived
008
INDUCTION Oil INTERLEUKIN 1 RECEPTOR ANTAGONIST IN KERATINOCYTES BY INFLAMMATORY CYTOKINES. T. Aokl. Institute for Advanced Skin Research Inc./Shiseido Center, Yokohama, Japan. We have previously repofied that content of IL-1 receptor antagonist (IL-lra) is markedly elevated in the stratum comeum of sun-exposed arca, UV-irradiated arca, and various inflammatory skin disorders. The purpose of this study is to examine the involvement of inflammatory cytokines on induction of an anti-inflammatory cytokine, IL-In+, in keratinocytes. Human keratinocytes, which were cultivated in the presence of mitomycin C-treated 333-12 feeder layer, were tteated with various cytokines, including IL-la, 8, TNF-a. TGF-a. 8, and IFN-I. Contents of IL-lra in kemdnocytes were examined by Western blotting or ELISA. IL-lra expression was enhanced markedly by IFN-1, and moderately by IL- la, 8, and TNF-a, but not by TGF-a and p. These results suggest that inflammatory cpokines produced by keratinocytes or infiltrating leukocytes can induce IL-lra in keratinocytes. Induction of IL-ha in kemtinocytes by inflammatory cytokincs may rcflcct a homeostalic response of the skin against various stimuli.
011
INTERLBUKIN (IL)-la AND INTERFERON-y INDUCE TUMOR NECROSIS FACTOR Oa PRODUCTION FROM HUMAN KERATINOCY’I’BS K. ~atsu~m. H. Fujlsawa, F. Otsuka. Dcpartmcnt of Dermatology, University of Tsukuba, Tsukuba, Japan. Tumor necrosis factor-a (TNF-a) is a proinflammatory cytokine and known to be produced by a wide variety of ceils including human keratinocytea (KCs). Altough ultraviolet B and lipopolysaccharlde are known to induce TNF-a production from human KCs, what types of cytokines induce TNF-a production was unclear. In the pnsent study, we have demonstrated that lntcrleukin (IL)-la and interferon (lFN)- y induced TNF-a, but no induction of TNF-a was observed with either IFN- a or IFN-8. Combined treatment with IL-la and IFNy induced TNF-a production synergistically. These results suggest that IL-la and IFN-y are a positive regulator for the production of TNF-a fmm human KCs and likely has an augmentative effect on skin inflammation.
009
EFFECT
OF AGING AND PHOTOAGING
ON TI-LE PRODUCTION
AND
EXPRESSION OF IL-lo AND IL-1 RECEPTOR ANTAGONIST IN RESPONSE TO SKIN IRRITANTS. l2.H. Sub. NC. Eun. 1.1. You Department of Dermatology, Seoul National Univeristy College of Medicine: Seoul, Korea Skin aging can be separately considered into photoaging and chronological aeinn. In spite of the expectation that there must be large difference in the &on& pattern to ir&nts, there has been no report io investigate skin aging by comparing prcduction and expression of cytokines in response to various stimuli. This study was done to know the change of the production and expression of IL-lo and IL-l receptor antagonist (IL.-h4 according to age groups with the treatment of UVB. TPA and
SLS. Monolayer keratinccyte cultures were performed using the skin from
newborn, young adults and aged volunteers. Production of cytokines by ELISA were generally decreased with the increase of age. IL-lrs production from forearm skin was significantly reduced compared with that from thigh skin. The cytokine production ratio of irritants-treated group to age-matched control group showed the decrease in case of IL-l% according to skin aging. These ratios were sometimes significantly different between forearm and thigh. The results of mRNA expressions by RT-PCR were diverse. These results indicated that the response patterns with skin aging were various according to the kinds of stimuli. They also suggested that photoaged skin and chronologically aged skin are much different in the production and expression of cytokines.
012
THE BFFECN OF INTERFERONS ON INTERLEUKlN(IL)d AND IL-8 PRODUCnON FROM HUMAN KERATINOCYTES. H. Fu’isawa K Matsuura, F. Otsuka. Department of Dermatology, University+rie o suku a,
~ba
Abstracts
Jepm.
have pleiotrophlc effects including the ability Intcrfemns (IFI%) to induce Interleukln (IL)-6 and IL-8 productions in several cell types. IL-6 and IL-8 are proinflammatov cytoklnes and known to be produced by a wide variety of cells including human keratlnocyte-s. In the present study, we sought to examine the effects of JFNs on IL-6 and IL-8 production from human keratinocytes. IFN-1 induced IL-6, and IL-8 production dose-dependently, but no ihducrion of IL-6 or IL-8 was observed with either IF% a or tFN-E. Combined treatment with IFN-y and IL-la Induced 6-7-fold higher levels of IL-6 than ILla alone. Combined tmatment with IFNq and TNF-a induced 1 I-12-fold higher levels than TNFa alone. The same treatments induced 34-fold higher levels of IL-8 in both cases. These. results suggest that IFN-y is a positive regulator for the production of IL-6 and IL-8 from human keratinocytes and likely has an augmentative effect on skin inflammation.
EFFECT OF STEM CELL FACTOR ON MAST CELL SURVIVAL AND CELL PROLIFERATION IN TRANSPLANTED NEUROFIBROMA IN NUDE MICE.T Demitsu. Department of Dermatology, Jichi Medical School, Tocbigi-ken, Japan Stem cell factor (SCF) plays an important role in the mast cell (MC) prolifemtion and development. However, little has been known the role of SCF on fully matured human skin mast cell (HSMC) in vitro and in vivo. We studied the effects of exogenous SCF on HSMCs in transplanted neurotibroma in nude mice and also examined the cell proliferation of the neurofibmma. Small pieces of neumfibroma in a patient with von Recklinghauscn’s disease were transplanted into the subcutis of nude mice. SCF (10 ng,lOOng) was injected around the neurotibroma tissues. MCs in transplanted neurofibmma injected with vehicle showed decreased in number when compared to those in neurofibroma before transplantation. Injection with SCF recovered MC number in neumfibroma tissue up fo the pre-transplantation level. Injection with SCF increased PCNA-positive cells in transplanted neumfibroma. From these findings HSMC is still capable of responding to SCF in vivo and SCF may play some role in increased MC number of cutaneous neumtibroma. In addition the growth of neurotibroma may relate fo the MC number in von Recklingbausen’s disease.