scholarly journals Fatty acid-mediated inhibition of IL-12 production by murine macrophages is independent of PPARγ

2004 ◽  
Vol 91 (5) ◽  
pp. 733-739 ◽  
Author(s):  
Meijuan Zhang ◽  
Kevin L. Fritsche

Our laboratory has reported that n-3 PUFA can reduce host resistance to Listeria infection, in part, by impairing in vivo IL-12 biosynthesis. Recently, PUFA were shown to be ligands for PPAR, a novel family of nuclear receptors with three isoforms: PPARα, PPARδ/β and PPARγ. PPARγ is expressed in immune cells, such as T cells and macrophages. Two PPARγ agonists, 15-deoxy-Δ12,14-prostaglandin (PG) J2 and rosiglitazone, have been shown to have immunomodulatory activity in vitro, including inhibiting IL-12 biosynthesis. We hypothesized that n-3 PUFA inhibit IL-12 production through activating PPARγ. We used thioglycolate-elicited mouse peritoneal macrophages to study the effect of various fatty acids and their oxidized metabolites on in vitro IL-12 production. Our present results demonstrate that both n-3 and n-6 PUFA can reduce in vitro IL-12 biosynthesis, though less potently than 15-deoxy-PGJ2 and rosiglitazone. GW9662, a PPARγ antagonist, reversed the inhibitory effect of rosiglitazone, but not that of PUFA. Our present findings suggest that fatty acid-mediated inhibition of IL-12 production is independent of PPARγ.

2009 ◽  
Vol 6 (5) ◽  
pp. 387-392 ◽  
Author(s):  
Yinan Wang ◽  
Xueling Cui ◽  
Guixiang Tai ◽  
Jingyan Ge ◽  
Nan Li ◽  
...  

1987 ◽  
Vol 166 (6) ◽  
pp. 1912-1917 ◽  
Author(s):  
A H Warfel ◽  
D Zucker-Franklin ◽  
B Frangione ◽  
J Ghiso

Cystatin C (gamma-trace) was found to be a constitutively secreted protein of isolated human monocytes and mouse peritoneal macrophages, as well as the histiocytic lymphoma cell lines U937, P388D.1, and J774. This proteinase inhibitor is not uniquely secreted by monocytes/macrophages, but was also identified in the conditioned media from several primary cells, including brain cells, and diverse established cell lines. In vitro treatment of resident mouse peritoneal macrophages with either LPS or IFN-gamma caused a downregulation in cystatin C secretion. Elaboration of this protein was also diminished by macrophages that had been stimulated by thioglycollate in vivo, and treatment of these cells with LPS led to further decline. It is suggested that, under some inflammatory conditions, downregulation of cystatin C may contribute to tissue pathology.


2009 ◽  
Vol 255 (1-2) ◽  
pp. 69-75 ◽  
Author(s):  
Jing Zhou ◽  
Guixiang Tai ◽  
Haiyan Liu ◽  
Jingyan Ge ◽  
Ye Feng ◽  
...  

2011 ◽  
Vol 3 (3) ◽  
pp. 619-630 ◽  
Author(s):  
S. P. Pattanayak ◽  
P. M. Mazumder

In the present study, an attempt was made to screen immunomodulatory activity of the hydroalcoholic extract (HEDF) of Dendrophthoe falcata (L.f.) Ettingsh (Loranthaceae), an Indian Ayurvedic plant, on different arms of the immune system. HEDF was evaluated for immunological function by studying delayed type hypersensitivity (DTH) to sheep RBCs, nitric oxide (NO) release from murine peritoneal macrophages, phagocytic activity of polymorphonuclear (PMN) cells in vitro and reticuloendothelial system in vivo, plaque forming cell response of splenic lymphocytes to sheep erythrocytes, haemagglutination antibody titer and neutrophil adhesion test. Significant increase in NO production by mouse peritoneal macrophages was detected in culture supernatants indicated increased phagocytic activity of macrophages. After post oral administration of HEDF in three doses of 250, 475 and 950 mg/kg body weight, a significant increase in phagocytic activity of PMN cells/reticuloendothelial system, stimulation of neutrophil function and splenic antibody secreting cells, were also noticed. Stimulation of humoral immune response was further observed with elevation in haemagglutination antibody titer. Heightened DTH reaction suggested convincing evidence for activation of cellular immune system. Present study thus confirms the immunomodulatory activity of the hydroalcoholic extract of D. falcata and the immunomodulatory responses were found to be dose dependent manner.Keywords: Dendrophthoe falcata; Antibody titer; Neutrophil adhesion; Phagocytic activity.© 2011 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.doi:10.3329/jsr.v3i3.7655               J. Sci. Res. 3 (3), 629-640 (2011)


1980 ◽  
Vol 151 (1) ◽  
pp. 101-114 ◽  
Author(s):  
M J Pabst ◽  
R B Johnston

After in vitro exposure to lipopolysaccharide (LPS) or muramyl dipeptide (MDP), cultured resident mouse peritoneal macrophages were primed to display enhanced generation of superoxide anion (O2-) in response to stimulation by phorbol myristate acetate (PMA) or opsonized zymosan. Priming with LPS (1 microgram/ml) produced a sevenfold enhancement of PMA-stimulated O2- generation; priming was detected within 30 min and persisted for at least 4 d. Exposure to MDP (1 muM) primed the macrophages to double their O2- release; the response was first observed after 4 h and persisted for at least 3 d. The priming response was not observed with stereoisomers of MDP, which are inactive as adjuvants. LPS and MDP appeared to work directly on the macrophages rather than indirectly by interacting with adherent lymphocytes: (a) Addition of nonadherent cell populations that contained lymphocytes had no effect on the response. (b) The response was normal with cells from nude mice, which lack mature T lymphocytes. (c) Macrophages from C3H/HeJ mice, whose B lymphocytes fail to respond to LPS, were weak in their response to priming LPS; the addition of normal (C3Heb/FeJ) nonadherent cells had no effect on this weak response. (d) The macrophage-like cell line J774.1 also showed enhanced O2--generating capacity after a 4-h exposure to LPS or MDP. The O2--generating capacity of macrophages primed with LPS in vitro was equivalent to that previously observed with cells elicited in vivo by injection of LPS or activated by infection with Bacille Calmette-Guérin. The data suggest that previous exposure to bacterial products could prime macrophages to respond with increased production of toxic oxygen metabolites on contact with invading microorganisms or tumor cells.


2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Angela Maria Arenas Velásquez ◽  
Willian Campos Ribeiro ◽  
Vutey Venn ◽  
Silvia Castelli ◽  
Mariana Santoro de Camargo ◽  
...  

ABSTRACT Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the Leishmania genus. Despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. The high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. We report here the evaluation of a binuclear cyclopalladated complex containing Pd(II) and N,N′-dimethylbenzylamine (Hdmba) against Leishmania amazonensis. The compound [Pd(dmba)(μ-N3)]2 (CP2) inhibits promastigote growth (50% inhibitory concentration [IC50] = 13.2 ± 0.7 μM) and decreases the proliferation of intracellular amastigotes in in vitro incubated macrophages (IC50 = 10.2 ± 2.2 μM) without a cytotoxic effect when tested against peritoneal macrophages (50% cytotoxic concentration = 506.0 ± 10.7 μM). In addition, CP2 was also active against T. cruzi intracellular amastigotes (IC50 = 2.3 ± 0.5 μM, selective index = 225), an indication of its potential for use in Chagas disease therapy. In vivo assays using L. amazonensis-infected BALB/c showed an 80% reduction in parasite load compared to infected and nontreated animals. Also, compared to amphotericin B treatment, CP2 did not show any side effects, which was corroborated by the analysis of plasma levels of different hepatic and renal biomarkers. Furthermore, CP2 was able to inhibit Leishmania donovani topoisomerase 1B (Ldtopo1B), a potentially important target in this parasite. (This study has been registered at ClinicalTrials.gov under identifier NCT02169141.)


2016 ◽  
Vol 68 (2) ◽  
pp. 311-318 ◽  
Author(s):  
Yuanbo Zhu ◽  
Jun Zhu ◽  
Liang Zhao ◽  
Ming Zhang ◽  
Huiyuan Guo ◽  
...  

A probiotic strain Lactobacillus paracasei L9,which was isolated from human intestine, was investigated for its immunomodulatory activity in vivo. Results showed that L9 improved systemic immunity by enhancing the phagocytic activity of peritoneal macrophages, the proliferation ratio of splenocytes, the IgG level in the serum and the level of IgA in the mucosa. Further, L9induced theTh1-polarized immune response by elevating the IFN-?/IL-4 ratio in the mucosa. This effect was confirmed by the enhanced IL-12-inducing activity of macrophages after in vitro stimulation of L9. Also detected was increased expression of TLR-2mRNA in the mucosa. We predict that L9 could enhance innate immunity by activating TLR-2 in the mucosa, and enhance acquired immunity by promoting Th1 polarization through induced production of IL-12 by macrophages.


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