PMID- 16428068
OWN - NLM
STAT- MEDLINE
DCOM- 20090223
LR  - 20171116
IS  - 1567-5769 (Print)
IS  - 1567-5769 (Linking)
VI  - 6
IP  - 3
DP  - 2006 Mar
TI  - Accelerative effect of a selective cyclooxygenase-2 inhibitor on Fas-mediated 
      apoptosis in human neutrophils.
PG  - 334-41
AB  - Inflammatory stimuli, such as cytokines, can induce cyclooxygenase-2 (COX-2) 
      expression in neutrophils. Selective, anti-inflammatory COX-2 inhibitors have 
      been developed for patients with acute inflammatory diseases. Recent work has 
      shown that selective COX-2 inhibitors interfere with tumor cell growth. The 
      purpose of this study was to examine the capability of selective COX-2 inhibitors 
      on Fas-mediated apoptosis in cytokine-stimulated neutrophils. Tumor necrosis 
      factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor 
      (GM-CSF) enhanced prostaglandin E2 (PGE2) release through the induction of COX-2 
      in neutrophils. This effect was not seen with either interleukin (IL)-1beta or 
      IL-8. TNF-alpha-and GM-CSF-induced PGE2 release was blocked by the addition of 
      the selective COX-2 inhibitor, 
      N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide (NS-398; 1 microM). GM-CSF, 
      IL-1beta and IL-8 suppressed Fas-mediated apoptosis in neutrophils; however, this 
      effect was not seen with TNF-alpha. The anti-apoptotic effect of cytokines on 
      Fas-mediated neutrophil apoptosis was attenuated by the addition of NS-398 (100 
      microM). These results suggest that NS-398 operates via two distinct mechanisms 
      for regulating apoptosis and COX-2 activation in neutrophils. This distinction is 
      indicated by the difference in concentration of NS-398 required for acceleration 
      of Fas-mediated neutrophil apoptosis, and the inhibition of PGE2 synthesis. 
      Moreover, NS-398 suppressed the anti-apoptotic activity of IL-8 and IL-1beta, but 
      did not induce COX-2; therefore, the pro-apoptotic mechanism of the selective 
      COX-2 inhibitor may be unrelated to COX-2 activity. Thus, a selective COX-2 
      inhibitor may contribute to the reduction of acute inflammation through the 
      enhancement of neutrophil apoptosis.
FAU - Iwase, Masayasu
AU  - Iwase M
AD  - Department of Oral and Maxillofacial Surgery, Showa University School of 
      Dentistry, 2-1-1, Kitasenzoku, Ota-ku, Tokyo, 145-8515, Japan. 
      iwase@senzoku.showa-u.ac.jp
FAU - Takaoka, Sayaka
AU  - Takaoka S
FAU - Uchida, Makiko
AU  - Uchida M
FAU - Kondo, Gen
AU  - Kondo G
FAU - Watanabe, Hitoshi
AU  - Watanabe H
FAU - Ohashi, Masaru
AU  - Ohashi M
FAU - Nagumo, Masao
AU  - Nagumo M
LA  - eng
PT  - Journal Article
DEP - 20050902
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Cytokines)
RN  - 0 (FAS protein, human)
RN  - 0 (Nitrobenzenes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sulfonamides)
RN  - 0 (fas Receptor)
RN  - 123653-11-2 (N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Cyclooxygenase 2/biosynthesis/genetics
MH  - Cyclooxygenase 2 Inhibitors/*pharmacology
MH  - Cytokines/physiology
MH  - Dinoprostone/metabolism
MH  - Enzyme Induction/drug effects
MH  - Humans
MH  - Neutrophils/*drug effects/enzymology
MH  - Nitrobenzenes/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Sulfonamides/*pharmacology
MH  - fas Receptor/*physiology
EDAT- 2006/01/24 09:00
MHDA- 2009/02/24 09:00
CRDT- 2006/01/24 09:00
PHST- 2005/05/09 00:00 [received]
PHST- 2005/06/20 00:00 [revised]
PHST- 2005/08/19 00:00 [accepted]
PHST- 2006/01/24 09:00 [pubmed]
PHST- 2009/02/24 09:00 [medline]
PHST- 2006/01/24 09:00 [entrez]
AID - S1567-5769(05)00241-9 [pii]
AID - 10.1016/j.intimp.2005.08.017 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2006 Mar;6(3):334-41. doi: 10.1016/j.intimp.2005.08.017. 
      Epub 2005 Sep 2.