PMID- 19776225
OWN - NLM
STAT- MEDLINE
DCOM- 20100503
LR  - 20100620
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 298
IP  - 5
DP  - 2010 May
TI  - Glucocorticoid reamplification within cells intensifies NF-kappaB and MAPK 
      signaling and reinforces inflammation in activated preadipocytes.
PG  - E930-40
LID - 10.1152/ajpendo.00320.2009 [doi]
AB  - Increased expression and activity of the intracellular 
      glucocorticoid-reactivating enzyme 11 beta-hydroxysteroid dehydrogenase type 1 
      (11 beta-HSD1) contribute to dysfunction of adipose tissue. Although the 
      pathophysiological role of 11 beta-HSD1 in mature adipocytes has long been 
      investigated, its potential role in preadipocytes still remains obscure. The 
      present study demonstrates that the expression of 11 beta-HSD1 in 
      preadipocyte-rich stromal vascular fraction (SVF) cells in fat depots from ob/ob 
      and diet-induced obese mice was markedly elevated compared with lean control. In 
      3T3-L1 preadipocytes, the level of mRNA and reductase activity of 11 beta-HSD1 
      was augmented by TNF-alpha, IL-1 beta, and LPS, with a concomitant increase in 
      inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 
      (MCP-1), or IL-6 secretion. Pharmacological inhibition of 11 beta-HSD1 and RNA 
      interference against 11 beta-HSD1 reduced the mRNA and protein levels of iNOS, 
      MCP-1, and IL-6. In contrast, overexpression of 11 beta-HSD1 further augmented 
      TNF-alpha-induced iNOS, IL-6, and MCP-1 expression. Moreover, 11 beta-HSD1 
      inhibitors attenuated TNF-alpha-induced phosphorylation of NF-kappaB p65 and 
      p38-, JNK-, and ERK1/2-MAPK. Collectively, the present study provides novel 
      evidence that inflammatory stimuli-induced 11 beta-HSD1 in activated 
      preadipocytes intensifies NF-kappaB and MAPK signaling pathways and results in 
      further induction of proinflammatory molecules. Not limited to 3T3-L1 
      preadipocytes, we also demonstrated that the notion was reproducible in the 
      primary SVF cells from obese mice. These findings highlight an unexpected, 
      proinflammatory role of reamplified glucocorticoids within preadipocytes in obese 
      adipose tissue.
FAU - Ishii-Yonemoto, Takako
AU  - Ishii-Yonemoto T
AD  - Division of Endocrinology and Metabolism, Department of Medicine and Clinical 
      Science, Kyoto University Graduate School of Medicine, 54, Shogoin Kawaharacho, 
      Sakyoku, Kyoto, 606-8507, Japan.
FAU - Masuzaki, Hiroaki
AU  - Masuzaki H
FAU - Yasue, Shintaro
AU  - Yasue S
FAU - Okada, Sadanori
AU  - Okada S
FAU - Kozuka, Chisayo
AU  - Kozuka C
FAU - Tanaka, Tomohiro
AU  - Tanaka T
FAU - Noguchi, Michio
AU  - Noguchi M
FAU - Tomita, Tsutomu
AU  - Tomita T
FAU - Fujikura, Junji
AU  - Fujikura J
FAU - Yamamoto, Yuji
AU  - Yamamoto Y
FAU - Ebihara, Ken
AU  - Ebihara K
FAU - Hosoda, Kiminori
AU  - Hosoda K
FAU - Nakao, Kazuwa
AU  - Nakao K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090923
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Cytokines)
RN  - 0 (Glucocorticoids)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
EIN - Am J Physiol Endocrinol Metab. 2010 Jul;299(1):E142
MH  - 11-beta-Hydroxysteroid Dehydrogenase Type 1/genetics/*metabolism
MH  - Adipocytes/*metabolism
MH  - Analysis of Variance
MH  - Animals
MH  - Blotting, Western
MH  - Cell Differentiation/genetics
MH  - Cytokines/genetics/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression Regulation, Enzymologic
MH  - Glucocorticoids/*genetics/metabolism
MH  - Inflammation/*genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/genetics/*metabolism
MH  - NF-kappa B/genetics/*metabolism
MH  - Obesity/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2009/09/25 06:00
MHDA- 2010/05/04 06:00
CRDT- 2009/09/25 06:00
PHST- 2009/09/25 06:00 [entrez]
PHST- 2009/09/25 06:00 [pubmed]
PHST- 2010/05/04 06:00 [medline]
AID - ajpendo.00320.2009 [pii]
AID - 10.1152/ajpendo.00320.2009 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2010 May;298(5):E930-40. doi: 
      10.1152/ajpendo.00320.2009. Epub 2009 Sep 23.