EVIDENCE THAT INTERLEUKIN-1 MEDIATES ITS EFFECTS ON BONE-RESORPTION VIA THE 80 KILODALTON INTERLEUKIN-1 RECEPTOR

被引:8
作者
GARRETT, IR
GUISE, TA
BONEWALD, LF
CHIZZONITE, R
MUNDY, GR
机构
[1] OSTEOSA INC,SAN ANTONIO,TX
[2] ROCHE INST MOLEC BIOL,NUTLEY,NJ 07110
关键词
INTERLEUKIN-1; RECEPTOR ANTIBODIES; BONE RESORPTION;
D O I
10.1007/BF00571333
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Interleukin-1 (IL-1) mediates its effects through two distinct receptors, one of 80 kilodaltons (80 kD) present in athymic lymphocytes and fibroblasts, and one of 60 kD present in cells of the monocyte-macrophage lineage. A novel monocyte cytokine in the IL-1 family which binds to both the 80 and the 60 kD receptors has been purified, cloned, and expressed. As the interleukin-1 receptor antagonist (IL-1ra) has been shown to inhibit bone resorption in organ culture, it is not clear whether these effects are mediated through the 80 or the 60 kD receptor. Recently, neutralizing antibodies (35F5) have been developed to the 80 kD receptor which inhibit IL-1 effects mediated through this receptor. To determine the importance of the 80 kD receptor to IL-1-mediated bone resorption, we used the neutralizing antibodies (35F5) to the 80 kD receptor to determine if they inhibited bone resorption stimulated by IL-1 in bone organ cultures. The 35F5 antibody blocked bone-resorbing activity due to IL-1 completely, and also blocked control or ''endogenous'' bone-resorbing activity present in murine bone organ cultures incubated in control media. The 35F5 antibody had no effect on bone resorption mediated by tumor necrosis factor (TNF), or parathyroid hormone (PTH). These data suggest that the availability of the 80 kD IL-1 receptor is required for osteoclastic bone resorption mediated by IL-1.
引用
收藏
页码:438 / 441
页数:4
相关论文
共 21 条
[1]   CYTOKINES AND CYTOKINE INHIBITORS OR ANTAGONISTS IN RHEUMATOID-ARTHRITIS [J].
AREND, WP ;
DAYER, JM .
ARTHRITIS AND RHEUMATISM, 1990, 33 (03) :305-315
[2]   BOLUS INJECTIONS OF RECOMBINANT HUMAN INTERLEUKIN-1 CAUSE TRANSIENT HYPOCALCEMIA IN NORMAL MICE [J].
BOYCE, BF ;
YATES, AJP ;
MUNDY, GR .
ENDOCRINOLOGY, 1989, 125 (05) :2780-2783
[3]   EFFECTS OF INTERLEUKIN-1 ON BONE TURNOVER IN NORMAL MICE [J].
BOYCE, BF ;
AUFDEMORTE, TB ;
GARRETT, IR ;
YATES, AJP ;
MUNDY, GR .
ENDOCRINOLOGY, 1989, 125 (03) :1142-1150
[4]   PURIFICATION, CLONING, EXPRESSION AND BIOLOGICAL CHARACTERIZATION OF AN INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN [J].
CARTER, DB ;
DEIBEL, MR ;
DUNN, CJ ;
TOMICH, CSC ;
LABORDE, AL ;
SLIGHTOM, JL ;
BERGER, AE ;
BIENKOWSKI, MJ ;
SUN, FF ;
MCEWAN, RN ;
HARRIS, PKW ;
YEM, AW ;
WASZAK, GA ;
CHOSAY, JG ;
SIEU, LC ;
HARDEE, MM ;
ZURCHERNEELY, HA ;
REARDON, IM ;
HEINRIKSON, RL ;
TRUESDELL, SE ;
SHELLY, JA ;
EESSALU, TE ;
TAYLOR, BM ;
TRACEY, DE .
NATURE, 1990, 344 (6267) :633-638
[5]   2 HIGH-AFFINITY INTERLEUKIN-1 RECEPTORS REPRESENT SEPARATE GENE-PRODUCTS [J].
CHIZZONITE, R ;
TRUITT, T ;
KILIAN, PL ;
STERN, AS ;
NUNES, P ;
PARKER, KP ;
KAFFKA, KL ;
CHUA, AO ;
LUGG, DK ;
GUBLER, U .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (20) :8029-8033
[6]   PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION FROM COMPLEMENTARY-DNA OF A HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST [J].
EISENBERG, SP ;
EVANS, RJ ;
AREND, WP ;
VERDERBER, E ;
BREWER, MT ;
HANNUM, CH ;
THOMPSON, RC .
NATURE, 1990, 343 (6256) :341-346
[7]   PRODUCTION OF LYMPHOTOXIN, A BONE-RESORBING CYTOKINE, BY CULTURED HUMAN MYELOMA CELLS [J].
GARRETT, IR ;
DURIE, BGM ;
NEDWIN, GE ;
GILLESPIE, A ;
BRINGMAN, T ;
SABATINI, M ;
BERTOLINI, DR ;
MUNDY, GR .
NEW ENGLAND JOURNAL OF MEDICINE, 1987, 317 (09) :526-532
[8]   STIMULATION OF BONE-RESORPTION INVITRO BY A NON-PROSTANOID FACTOR RELEASED BY HUMAN-MONOCYTES IN CULTURE [J].
GOWEN, M ;
MEIKLE, MC ;
REYNOLDS, JJ .
BIOCHIMICA ET BIOPHYSICA ACTA, 1983, 762 (03) :471-474
[9]  
GOWEN M, 1986, J IMMUNOL, V136, P2478
[10]  
GOWEN M, 1986, J BONE MINER RES, V1, P469