3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) attenuates LPS-induced IL-8 expression by decreasing mRNA stability in THP-1 cells
- Authors
- Im, Jintaek; Kang, Seok-Seong; Yang, Jae Seung; Yun, Cheol-Heui; Yang, Young; Han, Seung Hyun
- Issue Date
- Mar-2008
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- heterocyclic amine; Trp-P-1; immunotoxicity; IL-8; chemokine; THP-1
- Citation
- TOXICOLOGY LETTERS, v.177, no.2, pp 108 - 115
- Pages
- 8
- Journal Title
- TOXICOLOGY LETTERS
- Volume
- 177
- Number
- 2
- Start Page
- 108
- End Page
- 115
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/14297
- DOI
- 10.1016/j.toxlet.2008.01.002
- ISSN
- 0378-4274
1879-3169
- Abstract
- Heterocyclic amines (HCAs), such as Trp-P-1, PhIP, and IQ, are notorious food-born carcinogens. This study examined the inhibitory effects of HCAs on the expression of interleukin-8 (IL-8), which is an important chemokine for the initiation of innate immune responses that function by recruiting immune cells to inflamed sites. Among HCA types tested, only Trp-P-1 showed a robust inhibition of the lipopolysaccharide (LPS)-induced IL-8 expression at both mRNA and protein levels in a human monocytic cell-line, THP-1. However, Trp-P-1 did not inhibit the DNA-binding abilities of the transcription factors NF-kappa B, AP-1, and NF-IL6, all of which are known to regulate IL-8 transcription. Meanwhile, treatment with actinomycin D facilitated the Trp-P-1-induced down-regulation of IL-8 expression in LPS-stimulated THP-1 cells, implying that the inhibition might be due to a decrease in the stability of IL-8 mRNA rather than an attenuation of IL-8 transcription. Furthermore, Trp-P-1 also inhibited phosphorylation of p38 MAP kinase, which is involved in the regulation of IL-8 mRNA stability. Exogenous addition of ionomycin rescued both the IL-8 protein levels and phosphorylation of p38 MAP kinase inhibited by Trp-P-1. Collectively, these results suggest that Trp-P-1 suppresses LPS-induced IL-8 production in human monocytic cells through down-regulation of an intracellular calcium/p38 MAP kinase-dependent pathway, leading to the reduction of IL-8 mRNA stability. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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