Inactivation of the IL-6 gene prevents development of multicentric Castleman's disease in C/EBP beta-deficient mice.
Castleman's disease is a lymphoproliferative disorder thought to be related to deregulated production of IL-6. We have previously shown that mice lacking the trans-acting factor C/EBP beta, a transcriptional regulator of IL-6 and a mediator of IL-6 intracellular signaling, develop a pathology nearly identical to multicentric Castleman's disease, together with increasingly high levels of circulating IL-6. We describe here how the simultaneous inactivation of both IL-6 and C/EBP beta genes prevents the development of pathological traits of Castleman's disease observed in C/EBP beta-deficient mice. Histological and phenotypic analysis of lymph nodes and spleen of double mutant mice did not show either the lymphoadenopathy and splenomegaly or the abnormal expansion of myeloid, B and plasma cell compartments observed in C/EBP beta-/- mice, while B cell development, although delayed, was normal. Our data demonstrate that IL-6 is essential for the development of multicentric Castleman's disease in C/EBP beta-/- mice.
Screpanti
I
I
Dipartimento di Medicino Sperimentale c Patologia, Università La Sapienza, Roma, Italy.
Musiani
P
P
Bellavia
D
D
Cappelletti
M
M
Aiello
F B
FB
Maroder
M
M
Frati
L
L
Modesti
A
A
Gulino
A
A
Poli
V
V
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D022762:CCAAT-Enhancer-Binding Proteins; D005871:Castleman Disease / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D015850:Interleukin-6 / Q000235:genetics*; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D010950:Plasma Cells / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins