Commercially available recombinant sonic hedgehog up-regulates Ptc and modulates the cytokine and chemokine expression of human macrophages: an effect mediated by endotoxin contamination?

Sonia J Wakelin, John L R Forsythe, O James Garden, Sarah E M Howie

Research output: Contribution to journalArticlepeer-review

Abstract

The Sonic hedgehog (Shh) signalling pathway plays an important role in developmental patterning and proliferation. Recent evidence suggests that Shh also plays a role in the development of the immune system. Here, we demonstrate that components of the Shh signalling pathway are expressed in human macrophages and that the receptor for Shh, Ptc, is up-regulated by a commercially available recombinant preparation of Shh (CArShh). Further, we report that the addition of CArShh up-regulates the production of IL-6, IL-8, MCP-1, IP-10, MIG and RANTES by macrophages, an effect enhanced by the presence of fetal calf serum in the culture medium. In contrast, TGF-beta, TNF-alpha, IL-1b, IL-12 and IL-10 production were not modulated by CArShh and VEGF was minimally up-regulated even in the presence of serum. The up-regulation of these cytokines and chemokines was abrogated by CD14 inhibition and polymixin B, but not reliably inhibited by the specific Shh pathway inhibitor cyclopamine. These results suggest that, although components of the Shh signalling pathway are expressed in macrophages, the modulation of macrophage cytokine and chemokine effector function seen in response to commercially available rShh results from low levels of endotoxin contained within the CArShh preparations employed to explore the effects of Shh in vitro.
Original languageEnglish
Pages (from-to)25-38
Number of pages14
JournalImmunobiology
Volume213
Issue number1
DOIs
Publication statusPublished - Feb 2008

Keywords

  • Antigens, CD14
  • Cytokines
  • Drug Contamination
  • Endotoxins
  • Hedgehog Proteins
  • Humans
  • Macrophages
  • Polymyxin B
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Recombinant Proteins
  • Signal Transduction
  • Up-Regulation
  • Veratrum Alkaloids

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