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Study on the Action by PAF on IL-1 Modulation in Alveolar Macrophages: Involvement of Endogenous Arachidonate Metabolites and Intracellular $Ca^{++}$ Mobilization

Lee, Ji-Hee   (Department of Physiology, College of Medicine, Ewha Womans UniversityUU0001056  ); Kim, Won-Ki   (Department of Pharmacology, College of Medicine, Ewha Womans UniversityUU0001056  ); Hah, Jong-Sik   (Department of Physiology, College of Medicine, Ewha Womans UniversityUU0001056  );
  • 초록

    Platelet-activating factor(PAF) enhanced interleukin-1(IL-1) activity by the interaction with a specific receptor in rat alveolar macrophages. In this study, we investigated the role of endogenous arachidonate metabolites and intracellular calcium mobilization in the PAF-induced IL-1 activity. Alveolar macrophages were preincubated with 5-lipoxygenase and cyclooxygenase inhibitors 30 min before the addition of PAF and lipopolysaccharide(LPS). After 24h culture, IL-1 activity was measured in the supernate of sample using the thymocyte proliferation assay. Inhibition of 5-lipoxygenase by nordihydroguaiaretic acid and AA-861 completely blocked the PAF-induced enhancement of IL-1 activity with $IC_{50}\;of\;2\;{\mu}M\;and\;5\;{\mu}M$ , respectively. In contrast, the inhibition of cyclooxygenase pathway by indomethacin and ibuprofen resulted in the potentiation in PAF-induced IL-1 activity with maximal effect at $1\;{\mu}M\;and\;5\;{\mu}M$ , respectively. In addition, leukotriene $B_4$ and prostaglandin $E_2$ production were observed in PAF-stimulated alveolar macrophage culture. As could be expected, 5-lipoxygenase and cyclooxygenase inhibitors abolished PAF- stimulated leukotriene $B_4$ and prostaglandin $E_2$ production, respectively. The effects of PAF on intracellular calcium mobilization in alveolar macrophages were evaluated using the calcium-sensitive dye fura-2 at the single cell level. PAF at any dose between $10^{-16}\;and\;10^{-8}$ M did not increase intracellular calcium. Furthermore, there was no effective change of intracellular calcium level when PAF was added to alveolar macrophages in the presence of LPS or LPS+LTB4, and 4, 24 and 48h after treatment of these stimulants. Together, the results indicate that IL-1 activity induced by PAF is differently regulated through subsequent induction of endogenous 5-lipoxygenase and cyclooxygenase pathways, but not dependent on calcium signalling pathway.


  • 주제어

    PAF .   IL-1 .   Alveolar macrophages .   Lipoxygenase inhibitors .   Cyclooxygenase inhibitors .   Leukotriene $B_4$ .   Prostaglandin $E_2$ .   Intracellular $Ca^{++}$ mobilization.  

 저자의 다른 논문

  • Lee, Ji-Hee (6)

    1. 1995 "Effects of In Vitro Exposure to Silica on Bioactive Mediator Release by Alveolar Macrophages" 대한생리학회지 = Korean journal of physiology 29 (1): 1~11    
    2. 1995 "Platelet-Activating Factor Potentiates the Activity of Respiratory Burst and Interleukin-1 in Rat Alveolar Macrophages" 대한생리학회지 = Korean journal of physiology 29 (2): 251~257    
    3. 1996 "Effects of Platelet-Activating Factor on Tumor Necrosis $Factor-_{\alpha}$ Production by Muramyl Dipeptide- or Silica-Stimulated Alveolar Macrophages" 대한생리학회지 = Korean journal of physiology 30 (1): 77~83    
    4. 1997 "Platelet-Activating Factor Enhances Interleukin-1 Activity by Alveolar Macrophages : Inhibition by PAF Specific Receptor Antagonists" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 1 (2): 201~208    
    5. 1998 "Inducible Nitric Oxide Synthase mRNA Expression and Nitric Oxide Production in Silica-Induced Acute Inflammatory Lung Injury" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 2 (2): 233~239    
    6. 1999 "Acute Pulmonary Responses in Vivo to Silica Complexed with $H^+$, $Zn^{2+}$, or $Fe^{3+}$" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 3 (2): 183~189    
  • Kim, Won-Ki (1)

  • 하종식 (13)

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