PMID- 18054895
OWN - NLM
STAT- MEDLINE
DCOM- 20080425
LR  - 20091119
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 75
IP  - 5
DP  - 2008 Mar 1
TI  - SK-126, a synthetic compound, regulates the production of inflammatory cytokines 
      induced by LPS in antigen-presenting cells.
PG  - 1054-64
AB  - A variety of mediators released by immune cells triggers or enhances specific 
      aspects of the inflammatory response. Dendritic cells (DCs) play an essential 
      role in the innate immune system by shaping the adaptive immune responses and by 
      controlling the production of cytokines in response to inflammatory stimuli. In 
      the present study, we investigated whether SK-126, a pyridine derivative based on 
      gentianine originated from a natural product, can affect the LPS-induced 
      inflammatory cytokine production in DC. Interestingly, treatment of mouse bone 
      marrow-derived dendritic cells (BMDCs) and the murine dendritic cell line, DC 
      2.4, with SK-126 completely suppressed LPS-induced TNF-alpha expression at both 
      transcriptional and protein levels. In contrast to TNF-alpha, SK-126 enhanced 
      IL-10 expression at both transcriptional and protein levels. To determine 
      signaling pathways involved in the regulation of inflammatory cytokines, we 
      examined the involvement of MAPK and the transcription factor, NF-kappaB. SK-126 
      enhanced ERK1/2 and p38 activation following LPS stimulation, but it did not 
      induce phosphorylation of SAPK/JNK and NF-kappaB. Also, STAT3 phosphorylation 
      after LPS stimulation was increased by SK-126 to a large extent. Using specific 
      inhibitors, we confirmed that SK-126 has dual effects in which it suppresses 
      TNF-alpha production and enhances IL-10 production via the up-regulation of 
      ERK1/2 and p38. Finally, LPS-induced inflammatory responses such as TNF-alpha 
      production in vivo were significantly reduced by treatment with SK-126. 
      Therefore, our findings suggest that SK-126 may be a useful drug candidate to 
      treat inflammatory diseases in which pro- or anti-inflammatory cytokines play a 
      significant role in their pathogenesis.
FAU - Kang, Kyeongah
AU  - Kang K
AD  - Department of Biological Science and the Research Center for Women's Diseases, 
      Sookmyung Women's University, Seoul 140-742, Republic of Korea.
FAU - Kim, Hyeree
AU  - Kim H
FAU - Kim, Keun Il
AU  - Kim KI
FAU - Yang, Young
AU  - Yang Y
FAU - Yoon, Do-Young
AU  - Yoon DY
FAU - Kim, Joo-Hyon
AU  - Kim JH
FAU - Ryu, Je-Ho
AU  - Ryu JH
FAU - Noh, Eun-Jung
AU  - Noh EJ
FAU - Jeon, Sun-Duck
AU  - Jeon SD
FAU - Lim, Jong-Seok
AU  - Lim JS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071104
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (2-ethyl-8-(4-fluorophenyl)-6-methyl-3,4-dihydro-2H-(2,7)naphthyridin-1-one)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Naphthyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/*drug effects/immunology
MH  - Interleukin-10/genetics/*immunology
MH  - Lipopolysaccharides
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Naphthyridines/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/*immunology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2007/12/07 09:00
MHDA- 2008/04/26 09:00
CRDT- 2007/12/07 09:00
PHST- 2007/09/03 00:00 [received]
PHST- 2007/10/24 00:00 [revised]
PHST- 2007/10/29 00:00 [accepted]
PHST- 2007/12/07 09:00 [pubmed]
PHST- 2008/04/26 09:00 [medline]
PHST- 2007/12/07 09:00 [entrez]
AID - S0006-2952(07)00726-5 [pii]
AID - 10.1016/j.bcp.2007.10.028 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2008 Mar 1;75(5):1054-64. doi: 10.1016/j.bcp.2007.10.028. Epub 
      2007 Nov 4.