+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Modulation of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, and granulocyte/macrophage colony-stimulating factor expression in human monocytes by an endogenous anxiogenic benzodiazepine ligand, triakontatetraneuropeptide: evidence for a role of prostaglandins



Modulation of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, and granulocyte/macrophage colony-stimulating factor expression in human monocytes by an endogenous anxiogenic benzodiazepine ligand, triakontatetraneuropeptide: evidence for a role of prostaglandins



Molecular Pharmacology 43(1): 64-69



Triakontatetraneuropeptide (TTN) is the major processing product of the endogenous anxiogenic peptide ligand of the benzodiazepine receptor, diazepam binding inhibitor. In the present study, we demonstrated by Northern blot analysis that the mRNA levels for tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, granulocyte/macrophage colony-stimulating factor, IL-6, and IL-8 were significantly increased after 4 hr of incubation of human monocytes with lipopolysaccharide (LPS) and TTN (10(-11) M), compared with cells incubated with LPS alone. Exposure of monocytes for 20 hr to LPS and TTN (10(-11) M) also stimulated TNF-alpha, IL-1 beta and granulocyte/macrophage colony-stimulating factor release by 80%, 110%, and 98%, respectively, relative to the response elicited by LPS alone. Smaller stimulatory effects were observed using the prototypic pharmacological peripheral benzodiazepine Ro5-4864 (10(-11) M) (55%, 72%, and 62%, assessed by means of specific enzyme immunoassays). In contrast, TTN and Ro5-4864 did not modulate LPS-induced IL-6 and IL-8 production. Treatment with the cyclooxygenase inhibitor indomethacin increased IL-1 beta and TNF-alpha secretion but not that of IL-6 or IL-8. The observed stimulatory effects of TTN and indomethacin were not additive. Taken together, these findings suggest a common mechanism of action for TTN and indomethacin, involving PG formation. In this respect, TTN inhibited prostaglandin (PG) E2 production by 30%. The fact that the observed modulatory effects correlated with PG levels suggests the existence of a second-messenger pathway associated with the peripheral-type benzodiazepine receptor. These results indicate that human TTN differentially modulates the LPS-induced expression of proinflammatory cytokines, and they further support the concept that this endogenous psychoactive peptide could be involved in physiological control of the inflammatory response.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 046706890

Download citation: RISBibTeXText

PMID: 8380885


Related references

Treatment of BCL-1 murine B-cell leukemia with recombinant cytokines. Comparative analysis of the anti-leukemic potential of interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), and their combination. Leukemia and Lymphoma 7(1-2): 79-86, 1992

Interleukin-4 inhibits granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha expression by human monocytes in response to polymethylmethacrylate particle challenge in vitro. Journal of Orthopaedic Research 17(6): 797-802, 1999

Treatment of bcl 1 murine b cell leukemia with recombinant cytokines comparative analysis of the anti leukemic potential of interleukin 1 beta il 1 beta interleukin 2 il 2 interleukin 6 il 6 tumor necrosis factor alpha tnfalpha granulocyte colony stimulant factor g csf granulocyte macrophage colony stimulating factor gm csf and their combination. Leukemia & Lymphoma 7(1-2): 79-86, 1992

Production of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor by human mononuclear cells stimulated with granulocyte-macrophage colony-stimulating factor. Blood 72(4): 1368-1374, 1988

Suppression of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and granulocyte-monocyte colony stimulating factor secretion from human monocytes by an extract of Poria cocos. Zhonghua Minguo Wei Sheng Wu Ji Mian Yi Xue Za Zhi 25(1): 1-11, 1992

Effects of interferon-alpha on the expression of interleukin 1-beta , interleukin 6 , granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha in acute myeloid leukemia blasts. Leukemia 6(11): 1155-1160, 1992

Effects of interferon-alpha (IFN) on the expression of interleukin 1-beta (IL-1), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF) in acute myeloid leukemia (AML) blasts. Leukemia 6(11): 1155-1160, 1992

Effects of macrophage-colony stimulating factor on human monocytes: induction of expression of urokinase-type plasminogen activator, but not of secreted prostaglandin E2, interleukin-6, interleukin-1, or tumor necrosis factor-alpha. Journal of Leukocyte Biology 53(6): 707-714, 1993

Expression of macrophage colony-stimulating factor (M-CSF), interleukin-6, (IL-6), interleukin-1 beta (IL-1 beta), interleukin-11 (IL-11) and tumour necrosis factor-alpha (TNF-alpha) in p53-characterised human ovarian carcinomas. European Journal of Cancer 33(13): 2246-2251, 1997

Regulation of prostaglandin secretion from epithelial and stromal cells of the bovine endometrium by interleukin-1 beta, interleukin-2, granulocyte-macrophage colony stimulating factor and tumor necrosis factor-alpha. Life Sciences 51(14): 1171-1176, 1992

Absence of tumor necrosis factor alpha, interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor expression but presence of IL-1beta, IL-8, and IL-10 expression in human monocytes exposed to viable or killed Ehrlichia chaffeensis. Infection and Immunity 64(10): 4211-4219, 1996

Effects of macrophage-colony stimulating factor on human monocytes: Induction of expression of urokinase-type plasminogen activator, but not of secreted prostaglandin E 2 , interleukin-6, interleukin-1, or tumor necrosis factor-a. Journal of Leukocyte Biology 53(6): 707-714, 1993

Circadian rhythmometry of serum interleukin-2, interleukin-10, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor in men. Chronobiology International 12(1): 19-27, 1995

Differential effects of granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor on tumor necrosis factor and interleukin-1 production in human monocytes. Journal of Clinical and Laboratory Immunology 32(4): 161-166, 1990

Potentiating effect of granulocyte-macrophage colony-stimulating factor on interleukin-1-induced thymocyte proliferation: evidence for an interleukin-2 and tumor necrosis factor-independent pathway. Lymphokine Research 9(2): 155-165, 1990