Effect of 1,24-dihydroxyvitamin D3 on the growth of cultured human keratinocytes

221

Symposium II: Psoriasis EPIDEzw!x

RE_TI”N OFGRUWItl AND DIFFtRWllTIATIVN OF W% AND PMlHIRTIC

T. KurOkl oeparrmnr. Japan

KtRAT1WYn.h

Of Cancer

&?ll

&search,

l"Stl.t"tE of rnduzal

xclence.

Tokyo,

OUCED

BY

1,x.25-DIHYDROXYVITAMIN D, MODULATES IA ANTIGEN EXPRESSION ININTERFERON-y AND PROSTAGLANDIN Ez PRODUCTION IN PAM 212 CELLS

M. Tan). A. Komura and T. Honkawa Department of Dermatology, Kobe Un,vers,ty Japan

School

of Med,c,ne.

Kobe,

Recent lnvestlgations suggest that a b~olaglcally active metabollte of v,+.amln Dz. l~,,Zi~d,hvdroxvv,tam~n 03 l1~.25(0~I~~~l. has an effect on the regulat?& of ,mm;ne &ponse and that k&at;n;;yte express,on of mayor h~stocampat~b~l?ty complex class II ant?gens may be Involved in ,mmune responses. S,nce ,t 1s reported that system,c and top,cal adm>n,strat,on of la.Z5(OH) 2 D effect,ve I" some patients w,th psonasls and the demonstratxan of act,vated T lymphocytes and HLA-DR+ ierat,nocytes 3" psor,at3c plaques suggests that delayed cellular ,mnxlne responses may play an important role ,n the pathogenesls of psonas,s. we ?nvest,gated the lu.Z5(OH) 2 D modulation of la ant,gen expresslan Induced by ?nterferan-y (IFN?) and prastagland,n Ez(PGEz) productjon ,n Pam 212 cells [spontaneously transformed mur?ne (BALE/c) kerat?nocyte cell l,ne]. lo-'or lOi'M la,25(OH) 2 D the same concentrations as physlologlcal levels of lu.ES(OH)zD, s,gn,flcantly decreased the levels of IFN-‘r-Induced Ia antigen expresslan in Pam 212 cells. Pam 212 cells produced PGE: and la.Z5(0H)zD~enhanced Pam 212 cell PGEz productIon I" a dose-dependent manner. However. 1 ug/ml of lndomethac7n did not abrogate the inh,b,tory effect of lu.P5(OH)zDian IFN-v ,nduct,on of Pam 212 cell la antxgen expressxon. These f,nd,ngs suggat that la.25(OH)iD~ may play a role in the regulat,on of immune response and that this regulat>on 1s important ,n terms of the role which keratlnocytes may play ,n the ,mm,,ne response. and may at least part,ally account for the effectiveness of l'd,25(OH)-03 for the treatment of psonas,s.

i 1s

3

J at

EFFECTS

OF RETINOIDS

ON DNA SYNTHESIS

Y.Hashimoto, N.Ohkuma, H.Ilzuka Department of Dermatology, Asahikawa

Medical

OF PIG

College,

EPIDERMIS

Asahlkawa,

Japan

We investigated effects of /arious retlnolds on the thymidlne incorporatjon of pjg epidermis, which were compared with their effects on the beta-adrenergic adenylate cyclase response and the epidermal superoxide dismutase(SOD) activity. Following 24h incubation with synthetic retinolds(RolO-1670 and E-51661, thymidine incorparatlan of epidermis was significantly decreased. The effect of RolO-1670 was more potent than that of E-5166. Following the same treatment, the beta-adrenerglc augm&tation effect of RolO-1670 was again more potent than E-5166 with slmllar effective doses to those of thymidlne Incorporation. Thus the inhibitory effect on the thymidine lncorporatlon was inversely correlated to the beta-adrenergic augmentation effect among these synthetic retinolds. On the other hand, physiologic retinoids(retino1 and retinolc acid) revealed no correlation between these two parameters. Although decreased SOD activity is reported to be associated with keratinocyte hyperproliferation, the enzyme activity was unaffected in the retinold-treated hypoprollferative epidermis.