PMID- 12818375
OWN - NLM
STAT- MEDLINE
DCOM- 20030731
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 66
IP  - 1
DP  - 2003 Jul 1
TI  - Potentiation of tumor necrosis factor-alpha expression by YC-1 in alveolar 
      macrophages through a cyclic GMP-independent pathway.
PG  - 149-56
AB  - Using cultured rat alveolar NR 8383 macrophages, this study investigated the 
      effect of YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole], a soluble 
      guanylyl cyclase (sGC) activator, on the production of tumor necrosis 
      factor-alpha (TNF alpha). YC-1 enhanced lipopolysaccharide and interferon-gamma 
      (LPS/IFN gamma)-induced TNF alpha formation in a concentration- and 
      time-dependent fashion. YC-1 also caused an increasing effect on the TNF alpha 
      mRNA level, suggesting that the transcriptional process was involved. However, 
      further studies suggested that cyclic GMP did not mediate the potentiation of 
      YC-1 on TNF alpha release, because (a) the sGC inhibitor and the protein kinase G 
      inhibitor failed to block the effect; and (b) the cyclic GMP analogues, on the 
      contrary, concentration-dependently diminished LPS/IFN gamma-induced TNF alpha 
      synthesis. In agreement with this finding, YC-1 produced changes in cell function 
      but no changes in cyclic GMP and cyclic AMP levels or sGC activity. Pretreatment 
      of the cells with cyclooxygenase inhibitors, a p38 mitogen-activated protein 
      kinase inhibitor, a mitogen-activated protein kinase kinase (MEK) inhibitor, and 
      a tyrosine kinase inhibitor did not attenuate the potentiation of TNF alpha 
      release by YC-1. Cycloheximide prevented the YC-1-enhanced TNF alpha formation, 
      implying that new protein synthesis was required. Interestingly, protein kinase C 
      inhibitors enhanced the potentiation of YC-1 to a greater extent. Nevertheless, a 
      protein kinase C activator, phorbol 12-myristate 13-acetate, failed to suppress 
      the potentiation of TNFalpha production by YC-1. In summary, potentiation of TNF 
      alpha release by YC-1 in LPS/IFN gamma-activated alveolar macrophages is an 
      additional mode of action of this compound that is independent of the elevation 
      of cyclic GMP. Thus, caution needs to be used in attributing the YC-1-mediated 
      response to the activation of sGC.
FAU - Hwang, Tsong-Long
AU  - Hwang TL
AD  - Graduate Institute of Natural Products, College of Medicine, Chang Gung 
      University, Tao-Yuan, Taiwan, ROC. htl@mail.cgu.edu.tw
FAU - Wu, Chin-Chung
AU  - Wu CC
FAU - Guh, Jih-Hwa
AU  - Guh JH
FAU - Teng, Che-Ming
AU  - Teng CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indazoles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 154453-18-6 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cyclic AMP/metabolism
MH  - Cyclic GMP/*metabolism
MH  - Drug Interactions
MH  - Enzyme Inhibitors/*pharmacology
MH  - Guanylate Cyclase/metabolism
MH  - Indazoles/*pharmacology
MH  - Macrophages, Alveolar/*drug effects/enzymology/metabolism
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
EDAT- 2003/06/24 05:00
MHDA- 2003/08/02 05:00
CRDT- 2003/06/24 05:00
PHST- 2003/06/24 05:00 [pubmed]
PHST- 2003/08/02 05:00 [medline]
PHST- 2003/06/24 05:00 [entrez]
AID - S0006295203002028 [pii]
AID - 10.1016/s0006-2952(03)00202-8 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2003 Jul 1;66(1):149-56. doi: 10.1016/s0006-2952(03)00202-8.