Oxaprozin-induced apoptosis on CD40 ligand-treated human primary monocytes is associated with the modulation of defined intracellular pathways.

Publisher: Hindawi Pub. Corp Country of Publication: United States NLM ID: 101135740 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1110-7251 (Electronic) Linking ISSN: 11107243 NLM ISO Abbreviation: J Biomed Biotechnol Subsets: MEDLINE

Publication: 2006- : Cairo : Hindawi Pub. Corp.
Original Publication: Akron, Ohio : Hindawi Pub. Corp., [2001-

Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Apoptosis/*drug effects ; CD40 Ligand/*pharmacology ; Monocytes/*drug effects ; Propionates/*pharmacology; CD40 Ligand/blood ; Caspase 3/metabolism ; Cyclooxygenase Inhibitors/pharmacology ; Humans ; Inflammation/blood ; Mitogen-Activated Protein Kinases/blood ; Monocytes/cytology ; Monocytes/metabolism ; NF-kappa B p50 Subunit/blood ; Oxaprozin ; Phosphatidylinositol 3-Kinases/blood ; Phosphorylation ; Prostaglandin-Endoperoxide Synthases/blood ; Proto-Oncogene Proteins c-akt/blood ; Signal Transduction

The modulation of CD40L activity might represent a promising therapeutic target to reduce monocyte inflammatory functions in chronic diseases, such as rheumatoid arthritis. In the present study, we investigated the possible influence of nonsteroidal anti-inflammatory drugs (NSAIDs) on CD40L-induced monocyte survival. Monocytes were isolated from buffy coats by using Ficoll-Percoll gradients. Monocyte apoptosis was evaluated by fluorescence microscopy on cytopreps stained with acridine orange or using flow cytometry analysis of Annexin-V and Propidium Iodide staining. Akt and NF-kappaB activation was assessed using western blot. Caspase 3 activity was determined spectrophotometrically. Among different NSAIDs, only oxaprozin dose-dependently increased apoptosis of CD40L-treated monocytes. Oxaprozin pro-apoptotic activity was associated with the inhibition of CD40L-triggered Akt and NF-kappaB phosphorylation and the activation of caspase 3. In conclusion, our data suggest that oxaprozin-induced apoptosis in CD40L-treated human monocytes is associated with previously unknown cyclooxygenase (COX)-independent pathways. These intracellular proteins might be promising pharmacological targets to increase apoptosis in CD40L-treated monocytes.

Expert Opin Pharmacother. 2005 May;6(5):777-85. (PMID: 15934904)
J Biol Chem. 2007 Feb 23;282(8):5143-51. (PMID: 17182621)
Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693-7. (PMID: 8265610)
Cell Signal. 2005 Mar;17(3):355-63. (PMID: 15567066)
Int J Biochem Cell Biol. 2006;38(10):1654-61. (PMID: 16713323)
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9560-4. (PMID: 7568172)
Int J Immunopathol Pharmacol. 2005 Jul-Sep;18(3):403-15. (PMID: 16164824)
Eur J Biochem. 2000 Oct;267(19):6050-9. (PMID: 10998066)
Curr Med Res Opin. 2004 Aug;20(8):1279-90. (PMID: 15324531)
Immunopharmacology. 1983 Apr;5(4):259-65. (PMID: 6853143)
J Immunol Methods. 1991 Jun 3;139(2):271-9. (PMID: 1710634)
Rheumatology (Oxford). 2009 Jan;48(1):11-22. (PMID: 18927189)
Acta Pharmacol Sin. 2003 Jul;24(7):687-91. (PMID: 12852836)
Drugs. 1986 Oct;32(4):291-312. (PMID: 3536423)
Curr Med Res Opin. 2004 Aug;20(8):1275-7. (PMID: 15324530)
Curr Drug Targets Inflamm Allergy. 2004 Mar;3(1):1-9. (PMID: 15032637)
J Biol Chem. 2007 Jun 22;282(25):18307-18317. (PMID: 17459878)
Nat Rev Immunol. 2008 Oct;8(10):802-15. (PMID: 18825131)
Immunol Today. 1996 Oct;17(10):487-92. (PMID: 8908815)
J Immunol. 1995 Nov 15;155(10):4917-25. (PMID: 7594496)
Biochem Biophys Res Commun. 1999 Mar 24;256(3):449-55. (PMID: 10080918)
Cytokine. 2001 Nov 21;16(4):131-42. (PMID: 11792123)
Nat Rev Immunol. 2006 Jul;6(7):508-19. (PMID: 16778830)
Br J Pharmacol. 2009 May;157(2):294-306. (PMID: 19338579)
J Mol Cell Cardiol. 2009 May;46(5):612-20. (PMID: 19162037)
J Immunol. 1999 Aug 15;163(4):1755-62. (PMID: 10438906)
Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12790-5. (PMID: 17646662)
Blood. 2007 Oct 1;110(7):2545-55. (PMID: 17625065)
J Immunol. 1999 Jul 15;163(2):787-93. (PMID: 10395671)
Circ Res. 2001 Dec 7;89(12):1092-103. (PMID: 11739273)
Curr Opin Immunol. 1997 Aug;9(4):491-7. (PMID: 9287184)
Rheum Dis Clin North Am. 2004 Aug;30(3):603-25, x. (PMID: 15261344)
Immunol Today. 1997 Jun;18(6):272-7. (PMID: 9190112)
J Endotoxin Res. 2006;12(5):278-84. (PMID: 17059691)
Science. 1993 Sep 3;261(5126):1328-30. (PMID: 7689748)
Eur J Immunol. 2007 Jan;37(1):14-6. (PMID: 17183610)
Int J Immunopathol Pharmacol. 2003 Sep-Dec;16(3):225-31. (PMID: 14611725)
Blood. 2009 Jan 1;113(1):175-85. (PMID: 18827186)
Adv Immunol. 1996;61:1-77. (PMID: 8834494)
Annu Rev Immunol. 1998;16:111-35. (PMID: 9597126)
Curr Opin Rheumatol. 2007 May;19(3):289-95. (PMID: 17414958)
Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1918-28. (PMID: 17616749)
Eur J Pharmacol. 1998 Apr 17;347(1):87-94. (PMID: 9650852)
Free Radic Biol Med. 2001 Jan 15;30(2):161-9. (PMID: 11163533)

0 (Anti-Inflammatory Agents, Non-Steroidal)
0 (Cyclooxygenase Inhibitors)
0 (NF-kappa B p50 Subunit)
0 (NFKB1 protein, human)
0 (Propionates)
147205-72-9 (CD40 Ligand)
EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
EC 3.4.22.- (Caspase 3)
MHJ80W9LRB (Oxaprozin)

Date Created: 20090813 Date Completed: 20091029 Latest Revision: 20211020

20221213

PMC2723963

10.1155/2009/478785

19672323