Interferons and indoleamine 2,3-dioxygenase: Role in antimicrobial and antitumor effects

Summary Indoleamine 2,3-dioxygenase (IDO) is an interferon (IFN)-induced protein that initiates the metabolism of tryptophan along the kynurenine pathway. Although IDO can be induced by IFN- in many cell types, only mononuclear phagocytes have been shown to be induced to decyclize tryptophan by all three IFN classes. Since tryptophan is an essential amino acid necessary for a variety of metabolic processes, depletion of available tryptophan may be an important mechanism for control of rapidly-dividing microbial pathogens and tumors. The purpose of this review is to present evidence that documents the effects of IFN-induced IDO on prokaryotic and eukaryotic pathogens, as well as on a variety of tumor cell lines.     

Conversion of phenylalanine to toluene and 2-phenylethanol by the pine engraverIps pini (Say) (Coleoptera,Scolytidae)

Summary The pine engraver,Ips pini (Say), was found to produce toluene and 2-phenylethanol when boring into fresh pine logs. The hypotheses that phenylalanine is a precursor of these compounds and that beetles without their symbiotic microorganisms can perform these conversions were confirmed by treating wild and axencially-reared males and females topically with L-phenyl-d₅-alanine. Extracts of these beetles invariably contained deuterio-toluene, and extracts of males contained deuterio-2-phenylethanol as well.     

Interferons and indoleamine 2,3-dioxygenase: role in antimicrobial and antitumor effects

Indoleamine 2,3-dioxygenase (IDO) is an interferon (IFN)-induced protein that initiates the metabolism of tryptophan along the kynurenine pathway. Although IDO can be induced by IFN-gamma in many cell types, only mononuclear phagocytes have been shown to be induced to decyclize tryptophan by all three IFN classes. Since tryptophan is an essential amino acid necessary for a variety of metabolic processes, depletion of available tryptophan may be an important mechanism for control of rapidly-dividing microbial pathogens and tumors. The purpose of this review is to present evidence that documents the effects of IFN-induced IDO on prokaryotic and eukaryotic pathogens, as well as on a variety of tumor cell lines.     

Enhanced production of aggregation pheromones in four stored-product coleopterans feeding on methoprene-treated oats

Summary Production of aggregation pheromones by maleOryzaephilus surinamensis, O. mercator, Cryptolestes ferrugineus, andTribolium castaneum was enhanced by feeding on methoprene-treated oats, implicating juvenile hormone in control of pheromone production. Methoprene application to control insects in stored food products may cause enhanced pheromone production by these insects, thus drawing additional beetles into the treated product.Acknowledgments. We thank Dr. G. B. Staal of Zoëcon Corp. for a generous gift of methoprene. Particular thanks are due to J. Dodic for technical assistance. Research funded by the Natural Sciences and Engineering Research Council of Canada and the Science Council of British Columbia.     

Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands

Reciprocity of inflammation, oxidative stress and neovascularization is emerging as an important mechanism underlying numerous processes from tissue healing and remodelling to cancer progression. Whereas the mechanism of hypoxia-driven angiogenesis is well understood, the link between inflammation-induced oxidation and de novo blood vessel growth remains obscure. Here we show that the end products of lipid oxidation, ω-(2-carboxyethyl)pyrrole (CEP) and other related pyrroles, are generated during inflammation and wound healing and accumulate at high levels in ageing tissues in mice and in highly vascularized tumours in both murine and human melanoma. The molecular patterns of carboxyalkylpyrroles are recognized by Toll-like receptor 2 (TLR2), but not TLR4 or scavenger receptors on endothelial cells, leading to an angiogenic response that is independent of vascular endothelial growth factor. CEP promoted angiogenesis in hindlimb ischaemia and wound healing models through MyD88-dependent TLR2 signalling. Neutralization of endogenous carboxyalkylpyrroles impaired wound healing and tissue revascularization and diminished tumour angiogenesis. Both TLR2 and MyD88 are required for CEP-induced stimulation of Rac1 and endothelial migration. Taken together, these findings establish a new function of TLR2 as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.