Differential regulation of fibrinogen γ chain splice isoforms by interleukin-6

Chantelle M. Rein-Smith, Nathan W. Anderson, David Farrell

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Introduction: Fibrinogen is a major structural protein in blood clots, and is also a well-known acute phase reactant. The γ chain gene of fibrinogen has two alternative splice variants, γA and γ' chains. γ' fibrinogen constitutes about 7% of total fibrinogen. Total fibrinogen levels and γ' fibrinogen levels have been associated with cardiovascular disease, but the mechanisms regulating the production of the two isoforms are unknown. Several inflammatory cytokines are known to influence the production of total fibrinogen, but the role of cytokines in the production of γ' fibrinogen has not been examined. However, epidemiologic studies have shown an association between γ' fibrinogen levels and inflammatory markers in humans. Materials and methods: The expression of γ' fibrinogen and total fibrinogen by HepG2 liver cells was quantitated after treatment with interleukin-1β, transforming growth factor-β, tumor necrosis factor-α, and interleukin-6. Results: Interleukin-1β, transforming growth factor-β, and tumor necrosis factor-α, known down-regulators of total fibrinogen synthesis, also downregulate γ' fibrinogen synthesis in HepG2 cells. However, interleukin-6 differentially up-regulates the production of total and γ' fibrinogen, leading to a 3.6-fold increase in γA mRNA, but an 8.3-fold increase in γ' mRNA. Conclusions: These findings indicate that γ' fibrinogen is disproportionately up-regulated by inflammatory responses induced by interleukin-6.

Original languageEnglish (US)
Pages (from-to)89-93
Number of pages5
JournalThrombosis Research
Volume131
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Fibrinogen
Interleukin-6
Protein Isoforms
Hep G2 Cells
Transforming Growth Factors
Interleukin-1
Tumor Necrosis Factor-alpha
Cytokines
Messenger RNA
Acute-Phase Proteins
Epidemiologic Studies
Thrombosis
Cardiovascular Diseases
Up-Regulation
Down-Regulation

Keywords

  • Cytokines
  • Expression
  • Fibrinogen
  • Inflammation
  • Liver

ASJC Scopus subject areas

  • Hematology

Cite this

Differential regulation of fibrinogen γ chain splice isoforms by interleukin-6. / Rein-Smith, Chantelle M.; Anderson, Nathan W.; Farrell, David.

In: Thrombosis Research, Vol. 131, No. 1, 01.2013, p. 89-93.

Research output: Contribution to journalArticle

Rein-Smith, Chantelle M. ; Anderson, Nathan W. ; Farrell, David. / Differential regulation of fibrinogen γ chain splice isoforms by interleukin-6. In: Thrombosis Research. 2013 ; Vol. 131, No. 1. pp. 89-93.
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AB - Introduction: Fibrinogen is a major structural protein in blood clots, and is also a well-known acute phase reactant. The γ chain gene of fibrinogen has two alternative splice variants, γA and γ' chains. γ' fibrinogen constitutes about 7% of total fibrinogen. Total fibrinogen levels and γ' fibrinogen levels have been associated with cardiovascular disease, but the mechanisms regulating the production of the two isoforms are unknown. Several inflammatory cytokines are known to influence the production of total fibrinogen, but the role of cytokines in the production of γ' fibrinogen has not been examined. However, epidemiologic studies have shown an association between γ' fibrinogen levels and inflammatory markers in humans. Materials and methods: The expression of γ' fibrinogen and total fibrinogen by HepG2 liver cells was quantitated after treatment with interleukin-1β, transforming growth factor-β, tumor necrosis factor-α, and interleukin-6. Results: Interleukin-1β, transforming growth factor-β, and tumor necrosis factor-α, known down-regulators of total fibrinogen synthesis, also downregulate γ' fibrinogen synthesis in HepG2 cells. However, interleukin-6 differentially up-regulates the production of total and γ' fibrinogen, leading to a 3.6-fold increase in γA mRNA, but an 8.3-fold increase in γ' mRNA. Conclusions: These findings indicate that γ' fibrinogen is disproportionately up-regulated by inflammatory responses induced by interleukin-6.

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