Interleukin-1β modulates proinflammatory cytokine production in human epithelial cells

Mehmet A. Eskan, Manjunatha R. Benakanakere, Beate G. Rose, Ping Zhang, Jiawei Zhao, Panagiota Stathopoulou, Daisuke Fujioka, Denis F. Kinane

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Periodontitis is a chronic human inflammatory disease initiated and sustained by dental plaque microorganisms. A major contributing pathogen is Porphyromonas gingivalis, a gram-negative bacterium recognized by Toll-like receptor 2 (TLR2) and TLR4, which are expressed by human gingival epithelial cells (HGECs). However, it is still unclear how these cells respond to P. gingivalis and initiate inflammatory and immune responses. We have reported previously that HGECs produce a wide range of proinflammatory cytokines, including interleukin-6 (IL-6), IL-8, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha (TNF-α), and IL-1β. In this study, we show that IL-1α has a special role in the modulation of other inflammatory cytokines in HGECs challenged with P. gingivalis. Our results show that the increased production of IL-1β correlates with the cell surface expression of TLR4, and more specifically, TLR4-normal HGECs produce fourfold more IL-1β than do TLR4-deficient HGECs after challenge. Moreover, blocking the IL-1β receptor greatly reduces the production of "secondary" proinflammatory cytokines such as IL-8 or IL-6. Our data indicate that the induction of IL-1β plays an important role in mediating the release of other proinflammatory cytokines from primary human epithelial cells following challenge with P. gingivalis, and this process may be an inflammatory enhancement mechanism adopted by epithelial cells.

Original languageEnglish (US)
Pages (from-to)2080-2089
Number of pages10
JournalInfection and Immunity
Volume76
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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