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170 The regulation of CO-stimulatory molecules on Langerhans cells by various biological response modifiers, e.g., adjuvants and superantigens
JSID Abstracts/Journal
of Dermatological Science 10 (1995) 61-102
91
169
172
EPICUTANEOUS HAPTEN APPLlCATlON INDUCES A Y5 kDa TYPE IV COLLAGENASE (MMP-Y) SECRETION OF MURINE EPIDERMAL LANGERHANS CELLS Yasunobu Koba+u, Skin Can: R&D Division. R&D Headquarters, SUNSTAR Inc We c\;lnuned if some ol matns metalloproleuxases (MMP) an: invoh ed I” the mlgratmn prop&) of epidermal Iangerhans cells (LC). Using g&tinsubslratc en~mogram, ae found that murinc LCcnriched epdermal cells
FLARE-UP REACTION INDUCED BY STAPBVLDCOCCAL ENTERDTOXINB IN RURINE CONTACTHYPERSENSITIVITYREACTION: EFFECT OF REPEATEDCBAL-
obtained at ISh after 3% TNCB psnting sccrcti a Y5 kDa gelatmax Western blot analysis relealed that this gelatinase was a 95 kDa type IV collagena% the so called murme MMP-Y. DNCB and DNFB painting also stunulatcd a 95 kDa type IV cdlagenase secmt#on from L&enriched epidemxd cells B) contrast. SLS punting did not induced it These resulti suggest thal a 95 kDa 1) pe IV collagenase plays some unportant roles in the migmon capac!t) of LC. and tlus may allow LC to migrate through the basement membrane I” the mducbon phase oi the contact hypcr-scnslbuit).
LENCESWITH THE SPECIFIC HAI’TEN. Y. Natsuakl’.
K. Abe and Y Kitano
Department of Dematologv, Hyogo College of Medicine, Nishinomiy~. Japan. We previously reported that staDhylococca1 enterotoxin B (SEB) induced a flare-w Dhenownon in aurine contact hypersensitivity reaction (CHR) and that local imunological memory in CBR was intensified by repeated challenges with the specific hapten to the sane site. In this study, se investigated the effect of repeated challenges rith a haDten. dinitrofluorobenzene (DNFB). on SEB-induced flare-uo reaction in CHR. Mice were sensitized on day 0 and challenged on day 5 with DNFB. After that. DNlWchallenge ras repeated wee a reek. Ear swelling responses after SEBinjection were intensified in repeatedly challenged mice. In contrast. little reswose was found in SEB-anenized lice. These results
intensity tibility
suggest
that SEB-induced flare-tm
of the local immological to SEB in the muse.
I&N
reactio”
depends MI the
in CHR and the suscep-
170
173
THE REGULATION OF CO-STIMULATORY MOLECULES ON LANGERHANS CELLS BY VARIOUS BIOLOGICAL RESPONSE MODIFIERS, e.g., ADJUVANTS AND SUPERANTIGENS. s, * ~Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan Recently it has been demonstrated that co-stimulatoty molecules on antigen presenting cells regulate the ThlfTh2 development pathways. In this study, we analyzed the effects of various biological response modifiers, such as adjuvants and superantigens, on co-stimulatory molecule expression by epidermal Langerbans cells. Various biological response modifiers were injected subcutaneously into the ears of BALBlc mice, and the expression of class II MHC antigen and various co-stimulatory molecules were examined by flow cytometry. The injection of both complete and incomplete Freund’s adjuvant enhanced the expression of class 11MHC antigen, ICAM-I, 87-l and B7-2. In contrast, alum, which was used as an adjuvant for inducing Th2 response, can only up-regulate 87-2. The staphylococcal superantigens we examined, e.g., SEA, SEB, TSST-1, also augmented the expression of class II hfHC antigen as well as co-stimulatory molecules; although the magnitude of their augmentation induced by SEB was the greatest among them. These data suggest the possibility that biological response modifiers can modulate the expression of co-stimulatoty molecules on LC, which results in the regulation of ThliTh2 development.
STIMULATION OF PERIPHERAL BLOOD LYMPHOCY’IES WITH SKINCOLONIZED BACTERIA: SUPBRANTIGENIC AND NONY. SUPERANTIGENIC MACHANISMS. .. . .. Dq%utmc”t of W. H. W&ha T. Dermatology. HamDmatsu University School of Medicine, Hamamtsu, Japan; and tDepart~nt of Microbiology, School of Medicine, Shiga University of Medical Science. Shiga, Japan. Cutaneouscolonization of bancria, fmqaendy obsuved in patten~ whh sevaal skin diseases,is one of thecausative factors for exaeerbadonof theeruption. This deteriorating action of bacteriais suggestedto be “&iated by &.ased superpntigenictoxins tba~ activate T cetts am@ with tke disease.In mdez 10examinewbetbexski”solontzed bacteria stimulateIvnmbncvtes. ocrioheral htecd mononuclearcells (PBMC1 fran padma with atc&d&nat&s &l p&&is andiian normal subje& were &ured with mitomycin C (MMC)-@eatedbactertaisolated horn u&m’s lesionalskin. Superantigenproducing Smphyfocmcw (UYCIU(S.aurew) inducedmarked pmlifkration of $icnt’
171
174
THOR tmosIs FACTOR-~ Is A EDIATOR IN STAPHYL~C~CCALNEROTOXIN B-INDUCED SWPKESSION OF &URINE CONTACTHYPERSENSITIVITY KEACTION. K. Abe’. Y Natsuaki and Y Kitatm Departmnt of Denatoloex Hyogo CoI& of Medicine. Nishlnc&a. laDa”. Staphylococcal enterotoxin B (SEB) is one of bacterial exo-
IMh4JNOLOGICAL
toxins which have sunerantinen uronerties. Inlection of SEB can induce unresponsiven&s (an&j to SEB follo& transient stiw latiws of the particular T cell rmpulation. In this study, we investigated the immomdulaton effect of SEB in BALE/c mice. In in vitro study. normal spleen cells stiulated vith SBB shored significant proliferations and tuwr necrosis factor-a (m-12) omduction but spleen cells fmn SEB-inlected (anereized) lice did -wt show these r&.wnses. Injection of SEB or cultuie snwnatant of spleen cells with SEB sumressed the sensitization of wine cc&act hyuersensitlvitv reaction to dinitmfluombenzene (DNFB) and anti-TNF-a antibodies inhibited the suppressive effect of the super&ant.
In
contrast.
SEB-Injection
to
anerglzed
lice
ANALYSIS OF P?IENO~~ENON IN ATOUC
SKIN
Skin le.sio”s d ato& dermatitis wm cxamiwd for the cytoki”e expreasio” us@ RT-PCR me&d. The profile of mRNA for various
or
injection of culture snpernatant of wleen cells firm anergized plice rith SEB did not shw the swpressive effect. These results indicate that TNF-a is one of crucial mediators produced by SEBreswnding cells and way play a key role in the modulation of ClBL
live vari;rlla: zostu virua.Th& which WII mntwtiug vmi&
results au&a&l thatk tba atopic ski” lesii Use IL12 umdueed at the site d them
of Dermatological Science 10 (1995) 61-102
91
169
172
EPICUTANEOUS HAPTEN APPLlCATlON INDUCES A Y5 kDa TYPE IV COLLAGENASE (MMP-Y) SECRETION OF MURINE EPIDERMAL LANGERHANS CELLS Yasunobu Koba+u, Skin Can: R&D Division. R&D Headquarters, SUNSTAR Inc We c\;lnuned if some ol matns metalloproleuxases (MMP) an: invoh ed I” the mlgratmn prop&) of epidermal Iangerhans cells (LC). Using g&tinsubslratc en~mogram, ae found that murinc LCcnriched epdermal cells
FLARE-UP REACTION INDUCED BY STAPBVLDCOCCAL ENTERDTOXINB IN RURINE CONTACTHYPERSENSITIVITYREACTION: EFFECT OF REPEATEDCBAL-
obtained at ISh after 3% TNCB psnting sccrcti a Y5 kDa gelatmax Western blot analysis relealed that this gelatinase was a 95 kDa type IV collagena% the so called murme MMP-Y. DNCB and DNFB painting also stunulatcd a 95 kDa type IV cdlagenase secmt#on from L&enriched epidemxd cells B) contrast. SLS punting did not induced it These resulti suggest thal a 95 kDa 1) pe IV collagenase plays some unportant roles in the migmon capac!t) of LC. and tlus may allow LC to migrate through the basement membrane I” the mducbon phase oi the contact hypcr-scnslbuit).
LENCESWITH THE SPECIFIC HAI’TEN. Y. Natsuakl’.
K. Abe and Y Kitano
Department of Dematologv, Hyogo College of Medicine, Nishinomiy~. Japan. We previously reported that staDhylococca1 enterotoxin B (SEB) induced a flare-w Dhenownon in aurine contact hypersensitivity reaction (CHR) and that local imunological memory in CBR was intensified by repeated challenges with the specific hapten to the sane site. In this study, se investigated the effect of repeated challenges rith a haDten. dinitrofluorobenzene (DNFB). on SEB-induced flare-uo reaction in CHR. Mice were sensitized on day 0 and challenged on day 5 with DNFB. After that. DNlWchallenge ras repeated wee a reek. Ear swelling responses after SEBinjection were intensified in repeatedly challenged mice. In contrast. little reswose was found in SEB-anenized lice. These results
intensity tibility
suggest
that SEB-induced flare-tm
of the local immological to SEB in the muse.
I&N
reactio”
depends MI the
in CHR and the suscep-
170
173
THE REGULATION OF CO-STIMULATORY MOLECULES ON LANGERHANS CELLS BY VARIOUS BIOLOGICAL RESPONSE MODIFIERS, e.g., ADJUVANTS AND SUPERANTIGENS. s, * ~Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan Recently it has been demonstrated that co-stimulatoty molecules on antigen presenting cells regulate the ThlfTh2 development pathways. In this study, we analyzed the effects of various biological response modifiers, such as adjuvants and superantigens, on co-stimulatory molecule expression by epidermal Langerbans cells. Various biological response modifiers were injected subcutaneously into the ears of BALBlc mice, and the expression of class II MHC antigen and various co-stimulatory molecules were examined by flow cytometry. The injection of both complete and incomplete Freund’s adjuvant enhanced the expression of class 11MHC antigen, ICAM-I, 87-l and B7-2. In contrast, alum, which was used as an adjuvant for inducing Th2 response, can only up-regulate 87-2. The staphylococcal superantigens we examined, e.g., SEA, SEB, TSST-1, also augmented the expression of class II hfHC antigen as well as co-stimulatory molecules; although the magnitude of their augmentation induced by SEB was the greatest among them. These data suggest the possibility that biological response modifiers can modulate the expression of co-stimulatoty molecules on LC, which results in the regulation of ThliTh2 development.
STIMULATION OF PERIPHERAL BLOOD LYMPHOCY’IES WITH SKINCOLONIZED BACTERIA: SUPBRANTIGENIC AND NONY. SUPERANTIGENIC MACHANISMS. .. . .. Dq%utmc”t of W. H. W&ha T. Dermatology. HamDmatsu University School of Medicine, Hamamtsu, Japan; and tDepart~nt of Microbiology, School of Medicine, Shiga University of Medical Science. Shiga, Japan. Cutaneouscolonization of bancria, fmqaendy obsuved in patten~ whh sevaal skin diseases,is one of thecausative factors for exaeerbadonof theeruption. This deteriorating action of bacteriais suggestedto be “&iated by &.ased superpntigenictoxins tba~ activate T cetts am@ with tke disease.In mdez 10examinewbetbexski”solontzed bacteria stimulateIvnmbncvtes. ocrioheral htecd mononuclearcells (PBMC1 fran padma with atc&d&nat&s &l p&&is andiian normal subje& were &ured with mitomycin C (MMC)-@eatedbactertaisolated horn u&m’s lesionalskin. Superantigenproducing Smphyfocmcw (UYCIU(S.aurew) inducedmarked pmlifkration of $icnt’
171
174
THOR tmosIs FACTOR-~ Is A EDIATOR IN STAPHYL~C~CCALNEROTOXIN B-INDUCED SWPKESSION OF &URINE CONTACTHYPERSENSITIVITY KEACTION. K. Abe’. Y Natsuaki and Y Kitatm Departmnt of Denatoloex Hyogo CoI& of Medicine. Nishlnc&a. laDa”. Staphylococcal enterotoxin B (SEB) is one of bacterial exo-
IMh4JNOLOGICAL
toxins which have sunerantinen uronerties. Inlection of SEB can induce unresponsiven&s (an&j to SEB follo& transient stiw latiws of the particular T cell rmpulation. In this study, we investigated the immomdulaton effect of SEB in BALE/c mice. In in vitro study. normal spleen cells stiulated vith SBB shored significant proliferations and tuwr necrosis factor-a (m-12) omduction but spleen cells fmn SEB-inlected (anereized) lice did -wt show these r&.wnses. Injection of SEB or cultuie snwnatant of spleen cells with SEB sumressed the sensitization of wine cc&act hyuersensitlvitv reaction to dinitmfluombenzene (DNFB) and anti-TNF-a antibodies inhibited the suppressive effect of the super&ant.
In
contrast.
SEB-Injection
to
anerglzed
lice
ANALYSIS OF P?IENO~~ENON IN ATOUC
SKIN
Skin le.sio”s d ato& dermatitis wm cxamiwd for the cytoki”e expreasio” us@ RT-PCR me&d. The profile of mRNA for various
or
injection of culture snpernatant of wleen cells firm anergized plice rith SEB did not shw the swpressive effect. These results indicate that TNF-a is one of crucial mediators produced by SEBreswnding cells and way play a key role in the modulation of ClBL
live vari;rlla: zostu virua.Th& which WII mntwtiug vmi&
results au&a&l thatk tba atopic ski” lesii Use IL12 umdueed at the site d them