title: Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment.
abstract: IL-6-/- mice showed impaired leukocyte accumulation in subcutaneous air pouches. Defective leukocyte accumulation was not due to a reduced migratory capacity of IL-6-/- leukocytes and was associated with a reduced in situ production of chemokines. These observations led to a reexamination of the interaction of IL-6 with endothelial cells (EC). EC express only the gp130 signal transducing chain and not the subunit-specific IL-6R and are therefore unresponsive to IL-6. However, EC are responsive to a combination of IL-6 and soluble IL-6R as measured by the activation of STAT3, chemokine expression, and augmentation of ICAM-1. Activation by IL-6-IL-6R complexes was inhibited by an IL-6 receptor antagonist and potentiated by a superagonist. Hence, in vivo and in vitro evidence supports the concept that the IL-6 system plays an unexpected positive role in local inflammatory reactions by amplifying leukocyte recruitment.
authors.affiliation: Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Romano
authors.forename: M
authors.initials: M
authors.lastname: Sironi
authors.forename: C
authors.initials: C
authors.lastname: Toniatti
authors.forename: N
authors.initials: N
authors.lastname: Polentarutti
authors.forename: P
authors.initials: P
authors.lastname: Fruscella
authors.forename: P
authors.initials: P
authors.lastname: Ghezzi
authors.forename: R
authors.initials: R
authors.lastname: Faggioni
authors.forename: W
authors.initials: W
authors.lastname: Luini
authors.forename: V
authors.initials: V
authors.lastname: van Hinsbergh
authors.forename: S
authors.initials: S
authors.lastname: Sozzani
authors.forename: F
authors.initials: F
authors.lastname: Bussolino
authors.forename: V
authors.initials: V
authors.lastname: Poli
authors.forename: G
authors.initials: G
authors.lastname: Ciliberto
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators