TY - JOUR

T1 - Maggot secretions suppress pro-inflammatory responses of human monocytes through elevation of cyclic AMP

AU - van der Plas, Mariena

AU - Baldry, Mara

AU - T. van Dissel, J.

AU - N. Jukema, G.

AU - H. Nibbering, P.

N1 - OA

PY - 2009

Y1 - 2009

N2 - Aims/hypothesis Maggots of the blowfly Lucilia sericata areused for the treatment of chronic wounds. As monocytesmay contribute to the excessive inflammatory responses insuch wounds, this study focussed on the effects of maggotsecretions on the pro-inflammatory activities of these cells.Methods Freshly isolated monocytes were incubatedwith a range of secretions for 1 h and then stimulated withlipopolysaccharides (range 0–100 ng/ml) or lipoteichoic acid(range 0–5μg/ml) for 18 h. The expression of cell surfacemolecules, cytokine and chemokine levels in culture supernatants,cell viability, chemotaxis, and phagocytosis andkilling of Staphylococcus aureus were measured.Results Maggot secretions dose-dependently inhibited productionof the pro-inflammatory cytokines TNF-α, IL-12p40 and macrophage migration inhibitory factor bylipopolysaccharides- and lipoteichoic acid-stimulatedmonocytes, while enhancing production of the antiinflammatorycytokine IL-10. Expression of cell surfacereceptors involved in pathogen recognition remained unaffectedby secretions. In addition, maggot secretions altered thechemokine profile of monocytes by downregulating macrophageinflammatory protein-1β and upregulating monocytechemoattractant protein-1 and IL-8. Nevertheless, chemotacticresponses of monocytes were inhibited by secretions.Furthermore, maggot secretions did not affect phagocytosisand intracellular killing of S. aureus by human monocytes.Finally, secretions induced a transient rise in the intracellularcyclic AMP concentration in monocytes and Rp-cyclicAMPS inhibited the effects of secretions.Conclusions/interpretation Maggot secretions inhibit thepro-inflammatory responses of human monocytes througha cyclic AMP-dependent mechanism. Regulation of theinflammatory processes by maggots contributes to theirbeneficial effects on chronic wounds.

AB - Aims/hypothesis Maggots of the blowfly Lucilia sericata areused for the treatment of chronic wounds. As monocytesmay contribute to the excessive inflammatory responses insuch wounds, this study focussed on the effects of maggotsecretions on the pro-inflammatory activities of these cells.Methods Freshly isolated monocytes were incubatedwith a range of secretions for 1 h and then stimulated withlipopolysaccharides (range 0–100 ng/ml) or lipoteichoic acid(range 0–5μg/ml) for 18 h. The expression of cell surfacemolecules, cytokine and chemokine levels in culture supernatants,cell viability, chemotaxis, and phagocytosis andkilling of Staphylococcus aureus were measured.Results Maggot secretions dose-dependently inhibited productionof the pro-inflammatory cytokines TNF-α, IL-12p40 and macrophage migration inhibitory factor bylipopolysaccharides- and lipoteichoic acid-stimulatedmonocytes, while enhancing production of the antiinflammatorycytokine IL-10. Expression of cell surfacereceptors involved in pathogen recognition remained unaffectedby secretions. In addition, maggot secretions altered thechemokine profile of monocytes by downregulating macrophageinflammatory protein-1β and upregulating monocytechemoattractant protein-1 and IL-8. Nevertheless, chemotacticresponses of monocytes were inhibited by secretions.Furthermore, maggot secretions did not affect phagocytosisand intracellular killing of S. aureus by human monocytes.Finally, secretions induced a transient rise in the intracellularcyclic AMP concentration in monocytes and Rp-cyclicAMPS inhibited the effects of secretions.Conclusions/interpretation Maggot secretions inhibit thepro-inflammatory responses of human monocytes througha cyclic AMP-dependent mechanism. Regulation of theinflammatory processes by maggots contributes to theirbeneficial effects on chronic wounds.

U2 - 10.1007/s00125-009-1432-6

DO - 10.1007/s00125-009-1432-6

M3 - Journal article

C2 - 19575178

VL - 52

SP - 1962

EP - 1970

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 9

ER -