General nature of the STAT3-activated anti-inflammatory response.
Although many cytokine receptors generate their signals via the STAT3 pathway, the IL-10R appears unique in promoting a potent anti-inflammatory response (AIR) via STAT3 to antagonize proinflammatory signals that activate the innate immune response. We found that heterologous cytokine receptor systems that activate STAT3 but are naturally refractory (the IL-22R), or engineered to be refractory (the IL-6, leptin, and erythropoietin receptors), to suppressor of cytokine signaling-3-mediated inhibition activate an AIR indistinguishable from IL-10. We conclude that the AIR is a generic cytokine signaling pathway dependent on STAT3 but not unique to the IL-10R.
El Kasmi
Karim C
KC
Department of Infectious Diseases, St. Jude's Children's Research Hospital, Memphis, TN 38105, USA.
Holst
Jeff
J
Coffre
Maryaline
M
Mielke
Lisa
L
de Pauw
Antoine
A
Lhocine
Nouara
N
Smith
Amber M
AM
Rutschman
Robert
R
Kaushal
Deepak
D
Shen
Yuhong
Y
Suda
Takashi
T
Donnelly
Raymond P
RP
Myers
Martin G
MG
Alexander
Warren
W
Vignali
Dario A A
DA
Watowich
Stephanie S
SS
Ernst
Matthias
M
Hilton
Douglas J
DJ
Murray
Peter J
PJ
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D015151:Immunoblotting; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D053701:Receptors, Interleukin-10 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
D015850:Interleukin-6; D053701:Receptors, Interleukin-10; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10