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RSV‐infected airway epithelial cells cause biphasic up‐regulation of CCR1 expression on human monocytes
Author(s) -
Morrison Paul T.,
Thomas Lynette H.,
Sharland Mike,
Friedland Jon S.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1006611
Subject(s) - ccr1 , chemokine , biology , proinflammatory cytokine , cc chemokine receptors , monocyte , microbiology and biotechnology , receptor , chemokine receptor , cytokine , cycloheximide , immunology , inflammation , protein biosynthesis , biochemistry
Respiratory syncytial virus (RSV) infection can cause extensive airway inflammation, which is orchestrated by chemokines and their receptors. RSV‐infected epithelial cells secrete many cytokines and chemokines, but little is known about regulation of chemokine receptors on target cells. We investigated the effects of conditioned media (CM) from RSV‐infected epithelial cells on monocyte CCR1, CCR2, and CCR5 expression. RSV‐CM but not control‐CM stimulated a biphasic increase in cell‐surface CCR1, and levels peaked at 36 h and 96 h poststimulation. Similar CCR1 up‐regulation occurred on monocyte‐derived macrophages. Cytochlasin D and colchicine blocked both peaks of expression, demonstrating requirement of a functional cytoskeleton. Intracellular staining revealed little internal sequestration of CCR1 protein, and CCR1 up‐regulation was inhibited by actinomycin D and cycloheximide, indicating that both waves of RSV‐CM‐induced surface CCR1 expression were dependent on de novo transcription and protein synthesis. Cytokine‐neutralizing experiments showed that the effects of RSV‐CM were decreased by blocking TNF‐α (percent inhibition=51±2.3% at 36 h peak and 42±7.7% at 96 h peak) and to a lesser extent, IL‐1 (percent inhibition=32±7.2% at 36 h and 23±2.9% at 96 h). In summary, RSV‐CM causes a biphasic up‐regulation of surface CCR1 on monocytes, which is dependent on an intact cytoskeleton, requires new gene transcription and protein synthesis, and is mediated in part by the proinflammatory cytokines TNF‐α and IL‐1.