Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment.
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.
Romano
M
M
Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy.
Sironi
M
M
Toniatti
C
C
Polentarutti
N
N
Fruscella
P
P
Ghezzi
P
P
Faggioni
R
R
Luini
W
W
van Hinsbergh
V
V
Sozzani
S
S
Bussolino
F
F
Poli
V
V
Ciliberto
G
G
Mantovani
A
A
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
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