Regulated expression and release of the IL-1 decoy receptor in human mononuclear phagocytes.
The aim of this study was to investigate the expression and release of the IL-1 type II decoy receptor (R) in mononuclear phagocytes, which play a central role in immune and chronic inflammatory reactions. Human monocytes expressed both type I and type II R transcripts, the latter being two- to threefold more represented. By cross-linking and Ab blocking, the predominant surface IL-1-binding molecule was the decoy RII. IL-4, IL-13, and dexamethasone induced RI and RII transcripts and augmented the number of IL-1-binding sites with no modification of Kd values. The induced surface receptor was identified as the decoy RII. These stimuli induced the release of a soluble R with a m.w. of approximately 60 kDa, of which N-glycosylation contributed 22 kDa compared with 45 kDa released from polymorphonuclear leukocytes, of which N-glycosylation contributed 15 kDa. IL-13 and dexamethasone induced a release of 24 ng/ml/2 x 10(7) cells (from 8.7 to 43.2 ng/ml) and 25.6 ng/ml/2 x 10(7) cells (from 9.7 to 36.8 ng/ml) of decoy RII in 18 h, respectively (six donors). Thus, for instance, IL-13-treated (18 h) cells expressed 3.5 x 10(3) sites/cell and released 12 x 10(3) decoy RII/cell. The released decoy RII from monocytes bound IL-1apha and IL-1 receptor antagonist 30- and 2-fold less avidly than IL-1beta, respectively. In vitro-matured, monocyte-derived macrophages showed higher levels of surface expression and release of the IL-1 decoy RII. The results show that, on exposure to diverse molecules with anti-inflammatory properties, mononuclear phagocytes express and release copious amounts of a novel version of the soluble IL-1 decoy RII.
Colotta
F
F
Department of Immunology and Microbiology, Pharmacia Research Center, Nerviano, Italy.
Saccani
S
S
Giri
J G
JG
Dower
S K
SK
Sims
J E
JE
Introna
M
M
Mantovani
A
A
D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D006031:Glycosylation; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D053574:Receptors, Interleukin-1 Type II
D007375:Interleukin-1; D018793:Interleukin-13; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D015847:Interleukin-4; D003907:Dexamethasone