Identification of upstream signals regulating interleukin-6 gene expression during in vitro treatment of human B cells with pokeweed mitogen

Dharminder Chauhan, Surender Kharbanda, Hiroshi Uchiyama, Mitsuyoshi Urashima, Ruben C Fragoso, Jyoti Sen, Donald W. Kufe, Kenneth C. Anderson

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The present studies have characterized the regulation of interleukin-6 (IL-6) gene expression during pokeweed mitogen (PWM)-driven human B-cell differentiation. PWM induced an early and transient increase in the expression of immediatel-early response genes of the jun/fos leucine zipper family (c-jun, jun B, c-fos, and fos B). The induction of c-jun mRNA by PWM was concentration dependent. Nuclear run-on assays showed that PWM treatment is associated with an increased rate of c-jun gene transcription. The induction of c-jun mRNA precedes the induction of IL-6 gene expression and IL-6 secretion by the B cells. c-Jun antisense, but not sense, oligodeoxynucleotide (ODN) significantly decreases PWM-related B-cell (1) proliferation; (2) IL-6 mRNA induction; (3) IL-6 secretion; and (4) nuclear extract binding to AP-1 in electrophoretic mobility shift assay. In contrast, c-Fos antisense ODN did not effect either IL-6 mRNA induction or IL-6 secretion triggered in B cells by PWM. The results further show activation of c-Raf-1 kinase in PWM-treated B cells. Raf-1 acts upstream to mitogen- activated protein (MAP) kinase; therefore, studies were performed to assay for MAP kinase activation in these cells. The results show an increase in phosphorylation of myelin basic protein (MBP) and c-Jun 'Y' peptide in PWM- treated B cells. Taken together, these findings suggest that PWM is able to initiate an intracytoplasmic signaling cascade in normal human splenic B cells, which, at least in part, involves serine/threonine protein kinases. These results show transient induction of immediate-early response genes in B cells and support a potential role for the c-jun gene product in regulation of IL-6 transcription and secretion.

Original languageEnglish (US)
Pages (from-to)2243-2252
Number of pages10
JournalBlood
Volume84
Issue number7
StatePublished - Oct 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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    Chauhan, D., Kharbanda, S., Uchiyama, H., Urashima, M., Fragoso, R. C., Sen, J., Kufe, D. W., & Anderson, K. C. (1994). Identification of upstream signals regulating interleukin-6 gene expression during in vitro treatment of human B cells with pokeweed mitogen. Blood, 84(7), 2243-2252.