Iron tetrakis (N-methyl-4'-pyridyl) porphyrinato inhibits proliferative activity of thymocytes by blocking activation of p38 mitogen-activated protein kinase, nuclear factor-kappaB, and interleukin-2 secretion.
Iron tetrakis (N-methyl-4'-pyridyl) porphyrinato (FeTMPyP) has been demonstrated to be a potent scavenger of reactive oxygens and to have antiinflammatory activities. However, the effects of FeTMPyP on the function of T cells have not been illustrated. The objective of this study was to determine whether treatment of thymocytes with FeTMPyP inhibited the proliferative activity in response to various mitogens and, if so, to further characterize the mechanism of FeTMPyP immune modulation. The results indicate that treatment of thymocytes with FeTMPyP resulted in dose-dependent inhibition of thymocyte proliferation stimulated by concanawalin (Con) A-, Interleukin (IL)-1beta; or lipopdy socchande-exposed macrophage supernatant. FeTMPyP treatment also inhibited Con A- or IL-1beta-induced DNA-binding activity of NF-kappaB and IL-2 secretion by thymocytes. Both the p38 MAP kinase inhibitor SB203580 and the extracellular signal-regulated protein kinases inhibitor PD98059 blocked proliferative activity in Con A-stimulated thymocytes, while SB203580 but not PD98059 blocked nuclear factor (NF)-kappaB activation. FeTMPyP inhibited the activation and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in response to Con A. These data suggest that FeTMPyP downregulates the proliferative activity by inhibition of p38 MAPK activation, NF-kappaB activation, and IL-2 secretion during mitogenic stimulation of thymocytes. Therefore, further studies concerning the effects of FeTMPyP on the human diseases associated with both inflammatory disorders and immunologic overactivation are warranted.
Kang
Jihee Lee
JL
Department of Physiology, College of Medicine, Division of Cell Biology, Ewha Medical Research Center, Seoul 158-056, South Korea. jihee@mm.ewha.ac.kr
Lee
Hui Su
HS
Jung
Hae Jin
HJ
Kim
Hee Jae
HJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D005290:Ferric Compounds / Q000494:pharmacology* / Q000633:toxicity; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis*; D016328:NF-kappa B / Q000096:biosynthesis*; D013950:Thymus Gland / Q000166:cytology*; D048051:p38 Mitogen-Activated Protein Kinases
D005290:Ferric Compounds; D007376:Interleukin-2; D008665:Metalloporphyrins; D016328:NF-kappa B; D003208:Concanavalin A; C050951:tetrakis(N-methyl-4-pyridinium)yl-porphine iron(III) complex; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases