Interleukin 4 alone or in combination with interleukin 1 stimulates 3T3 fibroblasts to produce colony-stimulating factors.
Colony-stimulating activity (CSA) can be produced by fibroblasts when stimulated by interleukin 1 (IL-1). We show that like IL-1, interleukin 4 (IL-4) can stimulate 3T3 fibroblasts to produce CSA. Biological and molecular analyses show that a significant portion of the CSA is colony-stimulating factor 1 (CSF-1) and granulocyte colony-stimulating factor (G-CSF). CSF-1 production in cells stimulated with a combination of both IL-1 and IL-4 was greater than that observed when cells were stimulated with either cytokine alone. However, the data show a synergistic induction of the expression of high levels of G-CSF mRNA and protein in cells incubated in the presence of both IL-1 and IL-4. The concentration of G-CSF in supernatants from cells stimulated with both IL-1 and IL-4 was at least tenfold higher than that measured in supernatants harvested from cells stimulated with either IL-1 or IL-4 alone. Previous investigations have shown that IL-4 had direct effects on hematopoietic progenitor cell growth. The studies described herein indicate that IL-4 is also involved in the regulation of hematopoiesis in an indirect manner, that is, by playing a role in the regulation of hematopoietic growth factor production.
Tushinski
R J
RJ
Department of Experimental Hematology, Immunex Corporation, Seattle, Washington 98101.
Larsen
A
A
Park
L S
LS
Spoor
E
E
Williams
D E
DE
Mochizuki
D Y
DY
D000818:Animals; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism
D003115:Colony-Stimulating Factors; D007375:Interleukin-1; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4