Inhibition of cytokine-induced fractalkine production by bacterial invasion of human-dermal fibroblasts.
Fractalkine (FKN/CX3CL1) is an atypical chemokine, for which a major biological function has not yet emerged. However, recent data suggest a role in immune responses in the skin. In this study, we analyzed fractalkine (FKN) secretion by human-dermal fibroblasts after exposure to pro-inflammatory cytokines or to invasive and noninvasive strains of Escherichia coli. Incubation of fibroblasts with TNF-alpha and IL-1beta induced a delayed expression of soluble FKN, compared with the rapid secretion of other chemokines including IL-8 (CXCL8), monocyte chemotactic protein-1 (CCL2), and RANTES (regulated upon activation, normal T cell expressed and secreted; CCL5). TNF-alpha and IFN-gamma gamma were more potent at inducing FKN secretion than was IL-1beta. Very little FKN was detected on the cell surface. FKN was not detected after incubation with the bacteria, regardless of the strain used. In contrast, both invasive and noninvasive E. coli triggered the release of IL-8 and monocyte chemotactic protein-1 in a dose-response manner, whereas RANTES was produced only in response to the invasive strain. Finally, incubation of fibroblasts with the invasive strain of E. coli inhibited TNF-alpha- and IFN-gamma-induced production of FKN. These results demonstrate for the first time that human-dermal fibroblasts express FKN, and that the characteristics of FKN secretion are distinct from those of other chemokines produced by these cells during immune responses in the dermis. In addition, our data indicate that bacterial invasion of dermal fibroblasts actively modulates FKN expression.
Chemokine Biology Laboratory, Department of Molecular Biosciences, The University of Adelaide, South Australia, Australia.
Olivier Luc
OL
Fahy
Nicholas John
NJ
Coates
Shaun Reuss
SR
McColl
D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000096:biosynthesis* / Q000235:genetics; D004926:Escherichia coli / Q000472:pathogenicity*; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D007375:Interleukin-1; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha