PMID- 18336664
OWN - NLM
STAT- MEDLINE
DCOM- 20080829
LR  - 20131121
IS  - 1440-1746 (Electronic)
IS  - 0815-9319 (Linking)
VI  - 23 Suppl 1
DP  - 2008 Mar
TI  - Mechanisms for the anti-inflammatory effects of adiponectin in macrophages.
PG  - S50-3
LID - 10.1111/j.1440-1746.2007.05284.x [doi]
AB  - Adiponectin is an adipokine with potent anti-inflammatory properties. The 
      development of alcoholic liver disease is thought to involve increased 
      pro-inflammatory activity, mediated in part by the activation of hepatic 
      macrophages (Kupffer cells). Chronic ethanol feeding sensitizes hepatic 
      macrophages to activation by lipopolysaccharide (LPS), leading to increased 
      production of reactive oxygen species and tumor necrosis factor-alpha 
      (TNF-alpha). Adiponectin can normalize Toll-like receptor-4 (TLR-4) mediated 
      signaling in hepatic macrophages after ethanol feeding, likely contributing to 
      the hepatoprotective effect of adiponectin in the progression of alcoholic liver 
      disease. However, the mechanisms by which adiponectin suppress TLR-4 mediated 
      responses are not well understood. Using the macrophage-like cell line, RAW264.7, 
      we have investigated the molecular mechanisms by which adiponectin suppresses 
      LPS-stimulated TNF-alpha production. Globular adiponectin (gAcrp)-mediated 
      desensitization of LPS-stimulated responses in RAW264.7 macrophages was dependent 
      on the production of the anti-inflammatory cytokine interleukin (IL)-10. gAcrp 
      initially increased TNF-alpha expression in RAW264.7 macrophages; this TNF-alpha 
      then contributed to increased expression of IL-10. This initial gAcrp-mediated 
      increase in TNF-alpha production by macrophages was mediated via activation of 
      ERK1/2-->Egr-1 and nuclear factor (NF)-kappaB-dependent mechanisms. 
      gAcrp-stimulated IL-10 expression was also dependent on the phosphorylation of 
      cAMP response element-binding protein and the cAMP response element in the IL-10 
      promoter. In summary, these studies reveal a complex, integrated response of 
      macrophages to gAcrp. gAcrp initially activated signaling pathways considered to 
      be pro-inflammatory, with a subsequent increase in the expression of the potent, 
      anti-inflammatory cytokine, IL-10. Increased IL-10 expression was ultimately 
      required for the suppression of TLR4-mediated signaling by gAcrp.
FAU - Huang, Honglian
AU  - Huang H
AD  - Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA.
FAU - Park, Pil-Hoon
AU  - Park PH
FAU - McMullen, Megan R
AU  - McMullen MR
FAU - Nagy, Laura E
AU  - Nagy LE
LA  - eng
GR  - AA013868/AA/NIAAA NIH HHS/United States
GR  - AA11975/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - Australia
TA  - J Gastroenterol Hepatol
JT  - Journal of gastroenterology and hepatology
JID - 8607909
RN  - 0 (Adiponectin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Adiponectin/*physiology
MH  - Animals
MH  - Ethanol/pharmacology
MH  - Interleukin-10/biosynthesis
MH  - Macrophages/drug effects/*physiology
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
RF  - 41
EDAT- 2008/04/11 09:00
MHDA- 2008/08/30 09:00
CRDT- 2008/04/11 09:00
PHST- 2008/04/11 09:00 [pubmed]
PHST- 2008/08/30 09:00 [medline]
PHST- 2008/04/11 09:00 [entrez]
AID - JGH5284 [pii]
AID - 10.1111/j.1440-1746.2007.05284.x [doi]
PST - ppublish
SO  - J Gastroenterol Hepatol. 2008 Mar;23 Suppl 1:S50-3. doi: 
      10.1111/j.1440-1746.2007.05284.x.