title: Thioredoxin specifically cross-desensitizes monocytes to MCP-1.
abstract: Thioredoxin (Trx) is a protein disulfide oxidoreductase which can be secreted and acts as a cytokine. As we recently reported that Trx is chemotactic, we investigated whether it desensitizes monocytes or PMN to other chemokines. Preincubation for 15 min with Trx inhibited the chemotactic response of monocytes to MCP-1, but not to fMLP. This effect was independent of whether Trx was present during the chemotaxis assay or only during the preincubation. Preincubation (5 min) with Trx also inhibited the increase in intracellular Ca(2+) induced by MCP-1 in monocytes, but not that induced by fMLP. Preincubation with Trx did not affect the chemotactic response induced in PMN by IL-8. The inhibition of chemotactic and Ca(2+) responses to MCP-1 in monocytes was not due to a down-regulation of the MCP-1 receptor, as shown by receptor binding studies. The Ca(2+) response to MCP-1 was also inhibited by Trx in a CCR2-transfected cell line. It is suggested that Trx inhibits monocyte responses to chemokines by acting downstream of the chemokine receptors. Since there are high concentrations of circulating Trx in infection and inflammatory diseases, this might act as an inhibitor of monocyte migration in vivo.
authors.affiliation: Dompé S.p.A., L'Aquila, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pagliei
authors.forename: Pietro
authors.initials: P
authors.lastname: Ghezzi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bizzarri
authors.forename: Vilma
authors.initials: V
authors.lastname: Sabbatini
authors.forename: Giada
authors.initials: G
authors.lastname: Frascaroli
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Caselli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bertini
mesh_terms: D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013879:Thioredoxins / Q000187:drug effects*
chemical_list: D018932:Chemokine CCL2; D011994:Recombinant Proteins; D013879:Thioredoxins