YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Immunomodulatory Effect of cAMP-Elevating Agents on Macrophage- and T cell-Mediated Immune Responses

cAMP 증가 유도 약물의 대식세포- 및 T 세포-매개성 면역반응 조절작용

  • Rhee, Man-Hee (College of Veterinary Medicine, Kyungpook National University) ;
  • Cho, Jae-Youl (School of Bioscience and Biotechnology and Institute of Bioscience and Biotechnology, Kangwon National University)
  • 이만휘 (경북대학교 수의과대학) ;
  • 조재열 (강원대학교 BT학부대학 생물소재공학 및 생명공학연구소)
  • Published : 2007.02.28
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Abstract

To investigate the immunomodulatory roles of cyclic AMP (CAMP) on macrophage- and T lymphocyte-mediated immune responses, CAMP elevating agents were employed and carefully re-examined under the activation conditions of the cells. Various inhibitors tested dose-dependently blocked tumor necrosis factor (TNF)-${\alpha}$ production with IC$_{50}$ values ranged from 0.04 to 300 ${\mu}$M. Of the inhibitors, cAMP-elevating agents showed lower cytotoxicity assessed by lactate dehydrogenase (LDH) release, suggesting less toxic and more selective. In particular co-treatment of dbcAMP with a protein kinase C inhibitor staurosporine displayed the synergistic inhibition of TNF-${\alpha}$ production. The modulatory effect of dbcAMP on TNF-${\alpha}$ and nitric oxide (NO) was significantly affected by treatment time of dbcAMP. Thus, post-treatment of dbcAMP (three hours before LPS) abrogated dbcAMP's inhibitory activity and rather enhanced TNF-${\alpha}$ level up to 60%. In contrast, additional NO production was shown at the co-treatment of dbcAMP with LPS. Unlike simultaneous treatment of phorbol 12-myristate 13-acetate (PMA) and interferon (IFN)-${\gamma}$co-treatment, the combination of dbcAMP with other NO-inducing stimuli did not show drastic overproduction of NO. cAMP elevating agents also diminished splenocyte proliferation stimulated by concanavalin (Con) A, phytohemaglutinin A (PHA) and lipopolysaccharide (LPS). In addition, dbcAMP but not rolipram strongly suppressed CD8$^+$ T cells (CTLL-2). Finally, cAMP elevating agents were differentially involved in regulating CD98-mediated cell-cell adhesion. Thus, dbcAMP and rolipram significantly enhanced the cell-cell adhesion, whereas forskolin blocked. Therefore, our results suggest that CAMP elevating agents participate in various immune responses mediated by macrophages and T cells with a different fashion depending on cellular environments and activation signals.

Keywords

References

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