The effect of dexamcthasone on mRNA and protem synthesis of hpocortms (LCT) I, 2 and 5 has been investigated m W-937 cells A constltutwe expressIon of both mRNAs and protems was detected m undlfferentlated U-937 cells This constltutlve level was Increased time-and doscdependently by mcubatlon with phorbol myrlstate acetate (PMA) In U-937 cells dlffercntmted by 24 h mcubatlon with 6 n&ml PMA, dexdmethasone (DEX) (1 J!M for 16 h) caused an increased synthesis of the mRNA level of LCT-I and 2, but not of LCT-5, over the level Induced by PMA DEX had no effect m undlfferentlated cells Moreover, DEX stimulated the extracellular release of LCT-1 and 5, but not of LCT-2. and InhIbIted the release of PGEz and TXBZ only m the dlfferentlated U-937 cells These results suggest that the responsiveness of these cells to glucocoetlcolds IS dependent on the phase of cell dd-ferentlatlon The sckctwe release of hpocortms by dlfferentmtcd U-937 cells may explain, at least m part, the mhrbltlon by DEX of the prostanoid re!ease Llpocortm expresslon. Cell dlfferentlatlon, Dexamethasone, Elcosanold mhlbltlon
INTRODUCTIONLqmcortms have been defined as protems mduced by glucocortrcolds through a receptor-dependent mechanism which are able to inhibit phosphohpase A, enzyme activity [l]. This mhlbitlon results in. (I) a decreased release of pro-inflammatory hpld mctabohtes like prostaglandins, leukotrlenes and platelet-activating factor, (II) an anti-inflammatory action which munlcks the effect of glucocortlcolds (revtewed by Flower [2]) L~po-cortins belong to a large family of cafclum-and phosphohpid-bmdmg proteins which have been differently named.annexins. calpactins, chromobmdms, ancharms, cafcimcdins, endonexms, calefectrms, lnhlbltor of blood coagufdtlon, proteins I-III (for review see [3,4]) At the present, eight flpocortms have been identified and sequenced They share a common fourfold repeat structure [5] and are characterized by a 17-ammo acid consensus sequence which may be impflcated m the bmdmg to biomembranes [6].Llpocortms In this paper we have tegted the hypothesis that the mduction of tfle proteus by gfucoco~ trcolds is dcpcndVolume 291, number 2
FEBS LETTERSOctober 199 I