Bone marrow stromal cell regulation of B-lymphopoiesis. II. Mechanisms of hydroquinone inhibition of pre-B cell maturation.
Previous investigations from our laboratory have shown that the benzene metabolite, hydroquinone (HQ), inhibits B cell production by preventing the maturation of pre-B cells. Data presented in this paper demonstrate that HQ interrupts B-lymphopoiesis indirectly by inhibiting the production of interleukin-4 (IL-4) by fibroblastic stromal cells. HQ exposure of fibroblastic stromal cells (SCL-173 and SCL-160) did not affect IL-4 production by these cell lines at any dose tested. Addition of untreated bone marrow-derived macrophages to HQ-treated bone marrow stromal cells (heterogeneous population of fibroblastic cells and macrophages) reversed inhibition of IL-4 production. However, addition of HQ-treated macrophages was without effect. Our studies suggest that HQ inhibits macrophage production of IL-1, a potent inducer of IL-4 production by bone marrow fibroblastic stromal cells. Interruption of IL-1 release from macrophages mediates the observed inhibition of B lineage cell maturation.
King
A G
AG
Department of Pharmacology and Toxicology, West Virginia University Medical Center, Morgantown.
Landreth
K S
KS
Wierda
D
D
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D006410:Hematopoiesis / Q000187:drug effects*; D006873:Hydroquinones / Q000633:toxicity*; D007375:Interleukin-1 / Q000096:biosynthesis; D015847:Interleukin-4; D007378:Interleukins / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H
D006873:Hydroquinones; D007375:Interleukin-1; D007378:Interleukins; D008070:Lipopolysaccharides; D015847:Interleukin-4; D012321:DNA-Directed RNA Polymerases; C031927:hydroquinone