title: How the venom from the ectoparasitoid Wasp nasonia vitripennis exhibits anti-inflammatory properties on mammalian cell lines.
abstract: With more than 150,000 species, parasitoids are a large group of hymenopteran insects that inject venom into and then lay their eggs in or on other insects, eventually killing the hosts. Their venoms have evolved into different mechanisms for manipulating host immunity, physiology and behavior in such a way that enhance development of the parasitoid young. The venom from the ectoparasitoid Nasonia vitripennis inhibits the immune system in its host organism in order to protect their offspring from elimination. Since the major innate immune pathways in insects, the Toll and Imd pathways, are homologous to the NF-κB pathway in mammals, we were interested in whether a similar immune suppression seen in insects could be elicited in a mammalian cell system. A well characterized NF-κB reporter gene assay in fibrosarcoma cells showed a dose-dependent inhibition of NF-κB signaling caused by the venom. In line with this NF-κB inhibitory action, N. vitripennis venom dampened the expression of IL-6, a prototypical proinflammatory cytokine, from LPS-treated macrophages. The venom also inhibited the expression of two NF-κB target genes, IκBα and A20, that act in a negative feedback loop to prevent excessive NF-κB activity. Surprisingly, we did not detect any effect of the venom on the early events in the canonical NF-κB activation pathway, leading to NF-κB nuclear translocation, which was unaltered in venom-treated cells. The MAP kinases ERK, p38 and JNK are other crucial regulators of immune responses. We observed that venom treatment did not affect p38 and ERK activation, but induced a prolonged JNK activation. In summary, our data indicate that venom from N. vitripennis inhibits NF-κB signaling in mammalian cells. We identify venom-induced up regulation of the glucocorticoid receptor-regulated GILZ as a most likely molecular mediator for this inhibition.
authors.affiliation: Laboratory of Zoophysiology, Department of Physiology, Ghent University, Gent, Belgium.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Danneels
authors.affiliation: VIB Department of Medical Protein Research, Ghent University, Gent, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gerlo
authors.affiliation: Laboratory for Eukaryotic Gene Expression and Signal Transduction, Department of Physiology, Ghent University, Gent, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Heyninck
authors.affiliation: Laboratory for Eukaryotic Gene Expression and Signal Transduction, Department of Physiology, Ghent University, Gent, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Van Craenenbroeck
authors.affiliation: VIB Department of Medical Protein Research, Ghent University, Gent, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: De Bosscher
authors.affiliation: Laboratory for Eukaryotic Gene Expression and Signal Transduction, Department of Physiology, Ghent University, Gent, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Haegeman
authors.affiliation: Laboratory of Zoophysiology, Department of Physiology, Ghent University, Gent, Belgium.
authors.forename: Dirk C
authors.initials: DC
authors.lastname: de Graaf
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014688:Venoms / Q000494:pharmacology*; D014863:Wasps / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014688:Venoms; D048051:p38 Mitogen-Activated Protein Kinases