Interleukin 4 enhances osteoblast macrophage colony-stimulating factor, but not interleukin 6, production.
To determine if interleukin 4's (IL-4) recently discovered skeletal effects could be explained by its effects on osteoblasts, we have examined IL-4's impact on macrophage colony stimulating factor (M-CSF) and interleukin 6 (IL-6) secretion by the murine osteoblastic cell line MC3T3-E1. Interleukin-4 increased colony-forming activity in MC3T3 supernatants two-threefold with colony cytomorphology, cytohistochemistry, and blockade of the effect by anti-M-CSF antibody, indicating that the IL-4-induced activity was M-CSF. MC3T3 M-CSF supernatant activity increased in a time-dependent manner with positive IL-4 effects seen after a 24-hour exposure. The maximal IL-4 effective dose was 100 U/ml where conditioned media from IL-4-treated cells contained twofold more M-CSF than control cells (400 U/ml versus 200 U/ml M-CSF) as detected by a sandwich M-CSF ELISA. Northern blots showed that IL-4 (200 U/ml) rapidly increased steady-state M-CSF mRNA levels with maximal induction observed by 2 hours followed by a decline to near basal levels by 24 hours. IL-4 also dose dependently increased M-CSF mRNA levels with maximal induction (fourfold) seen at 100 U/ml IL-4. In contrast to its impact on MC3T3 M-CSF production, IL-4 (200 U/ml) did not stimulate MC3T3 IL-6 secretion whereas IL-1 (1 pM) stimulated a 500-fold increase in MC3T3 IL-6 release.(ABSTRACT TRUNCATED AT 250 WORDS)
Lacey
D L
DL
Department of Pathology, Jewish Hospital at Washington University, St. Louis, Missouri 63110.
Erdmann
J M
JM
Shima
M
M
Kling
S
S
Matayoshi
A
A
Ohara
J
J
Perkins
S L
SL
D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D016173:Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009000:Monocytes / Q000187:drug effects; D009693:Nucleic Acid Hybridization; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor