Prostaglandin I2 analogs inhibit proinflammatory cytokine production and T cell stimulatory function of dendritic cells

Weisong Zhou, Koichi Hashimoto, Kasia Goleniewska, Jamye F. O'Neal, Shaoquan Ji, Timothy S. Blackwell, Garret A. FitzGerald, Karine M. Egan, Mark W. Geraci, R. Stokes Peebles

Research output: Contribution to journalArticle

123 Scopus citations

Abstract

Signaling through the PGI2 receptor (IP) has been shown to inhibit inflammatory responses in mouse models of respiratory syncytial viral infection and OVA-induced allergic responses. However, little is known about the cell types that mediate the anti-inflammatory function of PGI2. In this study, we determined that PGI2 analogs modulate dendritic cell (DC) cytokine production, maturation, and function. We report that PGI 2 analogs (iloprost, cicaprost, treprostinil) differentially modulate the response of murine bone marrow-derived DC (BMDC) to LPS in an IP-dependent manner. The PGI2 analogs decreased BMDC production of proinflammatory cytokines (IL-12, TNF-α, IL-1α, IL-6) and chemokines (MIP-1α, MCP-1) and increased the production of the anti-inflammatory cytokine IL-10 by BMDCs. The modulatory effect was associated with IP-dependent upregulation of intracellular cAMP and down-regulation of NF-κB activity. Iloprost and cicaprost also suppressed LPS-induced expression of CD86, CD40, and MHC class II molecules by BMDCs and inhibited the ability of BMDCs to stimulate Ag-specific CD4 T cell proliferation and production of IL-5 and EL-13. These findings suggest that PGI2 signaling through the IP may exert anti-inflammatory effects by acting on DC.

Original languageEnglish (US)
Pages (from-to)702-710
Number of pages9
JournalJournal of Immunology
Volume178
Issue number2
DOIs
StatePublished - Jan 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zhou, W., Hashimoto, K., Goleniewska, K., O'Neal, J. F., Ji, S., Blackwell, T. S., FitzGerald, G. A., Egan, K. M., Geraci, M. W., & Peebles, R. S. (2007). Prostaglandin I2 analogs inhibit proinflammatory cytokine production and T cell stimulatory function of dendritic cells. Journal of Immunology, 178(2), 702-710. https://doi.org/10.4049/jimmunol.178.2.702