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p38 Mitogen-Activated Protein Kinase and Extracellular Signal-Regulated Kinase Regulate Nitric Oxide Production and Inflammatory Cytokine Expression in Raw Cells

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Abstract

Background: p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling are thought to have critical role in lipopolysaccharide (LPS)-induced immune response but the molecular mechanism underlying the induction of these signaling are not clear. Methods: Specific inhibitors for p38, SB203580, and for ERK, PD98059 were used. Cells were stimulated by LPS with or without specific MAPK inhibitors. Results: LPS activated inducible nitric oxide synthase (iNOS), subsequent NO productions, and pro-inflammatory cytokine gene expressions (TNF-α, IL-1β, IL-6, and IL-12). Treatment of both SB203580 and PD98059 decreased LPS- induced NO productions. Concomitant decreases in the expression of iNOS mRNA and protein were detected. SB203580 and PD98059 decreased LPS-induced gene expression of IL-1β and IL-6. SB203580 increased LPS-induced expression of TNF-α and IL-12, and reactive oxygen species production, but PD98059 had no effect. Conclusion: These results indicate that both p38 and ERK pathways are involved in LPS-stimulated NO synthesis, and expression of IL-1β and IL-6. p38 signaling pathways are involved in LPS-induced TNF-α and IL-12, and reactive oxygen species plays an important role in these signaling in macrophage.

참고문헌 (30)

  1. "Nitric oxide: pathophysiological mechanisms.", 57, pp.737~769 (1995)
  2. "Signal transduction from cell surface to nucleus in development and disease", pp.2581~2590 (1992)
  3. "a receptor for complexes of lipopolysaccharide", 249, pp.1431~249 1433 (1990)
  4. "kinases differentially regulate the lipopolysaccharide-mediated induction of inducible nitric oxide synthase and IL-12 in macrophages Leishmania phosphoglycans subvert macrophage IL-12 production by targeting ERK MAP kinase", 163, pp.6403~6412 (1999)
  5. "p38 but not p44", 42 mitogen-activated protein kinase is required for nitric oxide synthase induction mediated by lipopolysaccharide in RAW 264, 1999, pp.55, 481~488
  6. "Regulation of tumour necrosis factor alpha mRNA stability by the mitogen-activated protein kinase p38 signalling cascade", pp.57~61 (2000)
  7. "Role of mitogen-activated protein kinase cascades in mediating lipopolysaccharide-stimulated induction of cyclooxygenase-2 and IL-1 beta in RAW264 macrophages", 164, pp.3018~3025 (2000)
  8. "The p38", RK mitogen- activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor, pp.15, 1914~1923
  9. "NF- kappa B regulates the LPS-induced expression of interleukin 12 p40 in murine peritoneal macrophages roles of PKC", 204, pp.38~45 (2000)
  10. "Inhibition of extracellular signal-regulated kinase suppresses endotoxin-induced nitric oxide synthesis in mouse macrophages and in human colon epithelial cells", 294, pp.1188~1194 (2000)
  11. "IFN-gamma LPS induction of iNOS is modulated by ERK" (2001)
  12. "Cytotoxicity of inorganic mercury in murine T and B lymphoma cell lines involvement of reactive oxygen species Toxicol In Vitro 17", 17, pp.385~395 (2003), and cytokine gene expression
  13. "Mercury inhibits nitric oxide production but activates proinflammatory cytokine expression in murine macrophage differential modulation of NF-kappaB and p38 MAPK signaling pathways", 7, pp.67~74 (2002)
  14. "The role of p38 mitogen- activated protein kinase in IL-1 beta transcription", 162, pp.5367~5373 (1999)
  15. "Fumonisin hepatotoxicity is reduced in mice carrying the human tumour necrosis factor alpha transgene", 74, pp.238~248 (2000)
  16. "Evaluation of 2' 7'-dichlorofluorescin and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells", pp.348~355 (1993)
  17. "Effect of all-trans-retinoic acid on cytokine production in a murine macrophage cell line", 22, pp.693~706 (2000)
  18. "Redox control of cell death", 4, pp.405~414 (2002)
  19. "Role of oxidants in NF-kappa B activation and TNF- alpha gene transcription induced by hypoxia and endotoxin", 165, pp.1013~1021 (2000)
  20. "A synthetic inhibitor of the mitogen-activated protein kinase cascade", pp.7686~76869 (1995)
  21. "Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon- gamma", 179, pp.939~944 (1999)
  22. "Inhibition of extracellular signal-regulated kinase suppresses endotoxin-induced nitric oxide synthesis in mouse macrophages and in human colon epithelial cells", 294, pp.1188~1194 (2000)
  23. "Differential effects of p38- and extracellular signal-regulated kinase mitogen-activated protein kinase inhibitors on inducible ni-tric oxide synthase and tumor necrosis factor production in murine macrophages stimulated with Streptococcus pneumoniae", 185, pp.921~926 (2002)
  24. "P38 mitogen-activated protein kinase inhibitor SB203580 has a bi-directional effect on iNOS expression and NO production", 454, pp.115~123 (2002)
  25. "Inhibition of p38 MAP kinase during cellular activation results in IFN-gamma- dependent augmentation of IL-12 production by human monocytes", macrophages, 2001, pp.125, 64~70
  26. "Inhibition of MAP kinase kinase prevents cytokine and prostaglandin E2 production in lipopolysaccharide-stimulated monocytes", j immu(l 161), pp.5681~5686 (1998)
  27. "Cytokine mRNA decay is accelerated by an inhibitor of p38-mitogen-activated protein kinase", 48, pp.533~538 (1999)
  28. "The differential time-course of extracellular-regulated kinase activity correlates with the macrophage response toward proliferation or activation", pp.7403~7409 (2000)
  29. "Lipopolysaccharide-mediated reactive oxygen species and signal transduction in the regulation of interleukin-1 gene expression", pp.22131~22129 (2002)
  30. "Iron regulation of hepatic macrophage TNFalpha expression", 32, pp.309~313 (2002)

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