BACKGROUND: Phloroglucinol (PG), a polyphenolic compound, has been proposed to show free radical scavenging, anti-tumor, and immunomodulation effects on immune cells. In this study, we investigated PG for its immunological activity and their molecular mechanisms, specifically focusing on the functional activation of nuclear factor-kappaB (NFkappaB), an important transcription factor involved in the activation and differentiation of lymphocytes, and subsequent recruitment of murine lymphocytes. METHODS: We tested whether PG may contribute to the activation of immune response through the NFkappaB pathway by (3)H-thymidine incorporation assay, Western blot, intracellular cytokine assays and Electrophoretic mobility shift assay (EMSA) in murine lymphocytes. RESULTS: PG markedly enhanced the proliferation of lymphocytes by inducing the degradation and phosphorylation of IkappaB, which leads to the activation of NFkappaB p65. Also, PG induced the activation of mitogen-activated protein kinases (MAPKs) such as ERK1/2, JNK, and p38, upstream molecules of NFkappaB pathway. In addition, PG augmented the secretion of interleukin (IL)-2 in mature T lymphocytes and their production of IL-2. Furthermore, the application of TPCK significantly reduced the activation of lymphocytes by PG via inhibiting the NFkappaB activation. CONCLUSION: These results suggest that PG induces the activation of lymphocytes by inducing the proliferative activity and secretion of IL-2 through the classical NFkappaB. GENERAL SIGNIFICANCE: The effect of PG on lymphocyte activation was assayed for the first time. These results would also elucidate its underlying mechanism. Copyright 2010 Elsevier B.V. All rights reserved.
BACKGROUND:Phloroglucinol (PG), a polyphenolic compound, has been proposed to show free radical scavenging, anti-tumor, and immunomodulation effects on immune cells. In this study, we investigated PG for its immunological activity and their molecular mechanisms, specifically focusing on the functional activation of nuclear factor-kappaB (NFkappaB), an important transcription factor involved in the activation and differentiation of lymphocytes, and subsequent recruitment of murine lymphocytes. METHODS: We tested whether PG may contribute to the activation of immune response through the NFkappaB pathway by (3)H-thymidine incorporation assay, Western blot, intracellular cytokine assays and Electrophoretic mobility shift assay (EMSA) in murine lymphocytes. RESULTS:PG markedly enhanced the proliferation of lymphocytes by inducing the degradation and phosphorylation of IkappaB, which leads to the activation of NFkappaBp65. Also, PG induced the activation of mitogen-activated protein kinases (MAPKs) such as ERK1/2, JNK, and p38, upstream molecules of NFkappaB pathway. In addition, PG augmented the secretion of interleukin (IL)-2 in mature T lymphocytes and their production of IL-2. Furthermore, the application of TPCK significantly reduced the activation of lymphocytes by PG via inhibiting the NFkappaB activation. CONCLUSION: These results suggest that PG induces the activation of lymphocytes by inducing the proliferative activity and secretion of IL-2 through the classical NFkappaB. GENERAL SIGNIFICANCE: The effect of PG on lymphocyte activation was assayed for the first time. These results would also elucidate its underlying mechanism. Copyright 2010 Elsevier B.V. All rights reserved.