2,2'-bipyridyl based copper complexes down regulate expression of pro-inflammatory cytokines and suppress MAPKs in mitogen induced Peripheral blood mononuclear cells.
2,2'-bipyridyl based copper complex I: [CuC24H22N6O10] at 10 nM and complex Ia: [Cu2C32H43N8O3](PF6)4 at 7 nM exhibited 50% inhibition of lymphocyte proliferation and less than 20% cytotoxicity in peripheral blood mononuclear cells (PBMCs). Further, pro-inflammatory cytokines such as TNF-alpha and IL-1beta and pro-inflammatory mediator such as Nitric Oxide (NO) besides inducible Nitric Oxide Synthase (iNOS) were inhibited by the copper complexes. They also down regulated the expression of cyclooxegenase-2 (COX-2), yet another mediator of inflammation. Immunoblot analysis revealed the inhibitory effect of these complexes on phosphorylated forms protein kinases (MAPKs) such as ERK1/2, JNK, and p38 in mitogen induced PBMCs.
Rupesh
K R
KR
Department of Biotechnology, School of Life Sciences, Pondicherry University, Pondicherry, India.
Priya
A Moushumi
AM
Sundarakrishnan
B
B
Venkatesan
R
R
Lakshmi
B S
BS
Jayachandran
S
S
D015082:2,2'-Dipyridyl / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D007249:Inflammation / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D008934:Mitogens; D009942:Organometallic Compounds; D011453:Prostaglandins; D012333:RNA, Messenger; D009569:Nitric Oxide; D015082:2,2'-Dipyridyl; D003300:Copper; D007770:L-Lactate Dehydrogenase; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases