Interleukin-6 and CAAT/enhancer binding protein β-deficient mice act as tools to dissect the IL-6 signalling pathway and IL-6 regulation

Tonino Alonzi, Barbara Gorgoni, Isabella Screpanti, Alberto Gulino, Valeria Poli

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine playing important roles in immunity, hemopoiesis and inflammation. IL-6 signalling is known to involve the activation of two independent transcription factors: Stat3 (through phosphorylation by Jak kinases) and C/EBPβ (through activation of the ras pathway). In addition, C/EBPβ is believed to act as a transcriptional activator of the IL-6 gene itself. Making use of IL-6-deficient mice, we have recently demonstrated that IL-6 is essential for the induction of acute phase mRNAs in the liver upon localized tissue damage, but not upon systemically induced inflammation. Here we show that the defective mRNA induction is paralleled by a defective activation of Stat3, thus establishing a direct relationship between IL-6 function, Stat3 activation and acute phase genes induction. On the other hand, making use of C/EBPβ-deficient mice, we show that the induction of IL-6 by a variety of stimuli does not require C/EBPβ activity. In contrast to the predicted activating role of C/EBPβ, IL-6 levels are increased in the C/EBPβ-deficient mice, suggesting that C/EBPβ may act as a down-modulator of the IL-6 gene. Through the generation of C/EBPβ, IL-6 double mutant mice we show that IL-6 hyperproduction is responsible for the development of the Castleman's like lymphoproliferative disease described in the C/EBPβ-deficient mice, since the disorder is completely blocked by inactivating the IL-6 gene.

Original languageEnglish
Pages (from-to)144-156
Number of pages13
JournalImmunobiology
Volume198
Issue number1-3
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Immunology

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