PMID- 9548510
OWN - NLM
STAT- MEDLINE
DCOM- 19980420
LR  - 20171116
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 159
IP  - 11
DP  - 1997 Dec 1
TI  - IL-11 regulates macrophage effector function through the inhibition of nuclear 
      factor-kappaB.
PG  - 5661-70
AB  - Recombinant human IL-11 (rhIL-11) is an anti-inflammatory cytokine that can 
      reduce the production of inflammatory mediators such as TNF-alpha, IL-1beta, 
      IL-12, IL-6, and nitric oxide. Inhibition of proinflammatory cytokine production 
      from activated macrophages was associated with a reduction in the levels of 
      LPS-induced TNF-alpha, IL-1beta, IL-6, and IL-12 p40 mRNA. Analysis of rhIL-11 
      effects on transcription factors that activate proinflammatory cytokines 
      demonstrated that the level of LPS-induced NF-kappaB binding activity in the 
      nucleus of rhIL-11-treated peritoneal macrophages was significantly reduced. The 
      block to NF-kappaB nuclear translocation correlated with the ability of rhIL-11 
      to maintain or increase protein levels of the inhibitors of NF-kappaB, 
      IkappaB-alpha, and IkappaB-beta following LPS treatment. Furthermore, 
      rhIL-11-treatment of LPS macrophages resulted in significant elevation of 
      IkappaB-alpha and IkappaB-beta mRNA levels. These results suggest that the 
      anti-inflammatory activity of rhIL-11 is mediated in part by inhibition of 
      NF-kappaB-dependent transcriptional activation. Furthermore, these studies 
      demonstrate for the first time the regulation of IkappaB-beta by an 
      anti-inflammatory cytokine. Given the finding that inappropriate activation of 
      NF-kappaB contributes to multiple inflammatory conditions, the ability of rhIL-11 
      to inhibit the binding activity of this pleiotropic transcription factor 
      indicates that rhIL-11 has therapeutic potential in a wide range of diseases.
FAU - Trepicchio, W L
AU  - Trepicchio WL
AD  - Preclinical Molecular and Cellular Biology, Genetics Institute, Andover, MA 
      01810, USA. wtrepicchio@genetics.com
FAU - Wang, L
AU  - Wang L
FAU - Bozza, M
AU  - Bozza M
FAU - Dorner, A J
AU  - Dorner AJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cytokines)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I kappa B beta protein)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Interleukin-11)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - HM5641GA6F (oprelvekin)
SB  - IM
MH  - Animals
MH  - Cytokines/genetics/*metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Gene Expression
MH  - Humans
MH  - *I-kappa B Proteins
MH  - Inflammation/immunology
MH  - Interleukin-11/*pharmacology
MH  - Macrophage Activation
MH  - Macrophages, Peritoneal/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/*physiology
MH  - RNA, Messenger/metabolism
MH  - Recombinant Proteins/pharmacology
EDAT- 1998/04/21 00:00
MHDA- 1998/04/21 00:01
CRDT- 1998/04/21 00:00
PHST- 1998/04/21 00:00 [pubmed]
PHST- 1998/04/21 00:01 [medline]
PHST- 1998/04/21 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1997 Dec 1;159(11):5661-70.