scholarly journals Clindamycin Modulates Inflammatory-Cytokine Induction in Lipopolysaccharide-Stimulated Mouse Peritoneal Macrophages

2003 ◽  
Vol 47 (1) ◽  
pp. 363-367 ◽  
Author(s):  
Tetsuji Nakano ◽  
Kazufumi Hiramatsu ◽  
Kenji Kishi ◽  
Norio Hirata ◽  
Jun-ichi Kadota ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Peritoneal Macrophages ◽  
Cytokine Mrna ◽  
Necrosis Factor Alpha ◽  
Expression Levels ◽  
Cytokine Induction ◽  
Intracellular Expression ◽  
Factor Alpha ◽  
Mouse Peritoneal Macrophages ◽  
Necrosis Factor

ABSTRACT We investigated the mechanism by which clindamycin (CLI) modulates cytokine induction after lipopolysaccharide (LPS) stimulation. Although CLI decreased the intracellular expression levels of tumor necrosis factor alpha and interleukin 1β (IL-1β) and increased IL-6 expression in macrophages, cytokine mRNA expression levels were similar in CLI-treated and untreated groups. Our findings suggest that CLI modulates cytokine production in LPS-stimulated macrophages.

scholarly journals Lipopolysaccharide-induced selective priming effects on tumor necrosis factor alpha and nitric oxide production in mouse peritoneal macrophages.

1993 ◽  
Vol 177 (2) ◽  
pp. 511-516 ◽  
Author(s):  
X Zhang ◽  
D C Morrison
Keyword(s):  
Tumor Necrosis ◽  
Peritoneal Macrophages ◽  
Tnf Alpha ◽  
No Production ◽  
Necrosis Factor Alpha ◽  
Priming Effects ◽  
Alpha Production ◽  
Factor Alpha ◽  
Mouse Peritoneal Macrophages ◽  
Necrosis Factor

Preculture of thioglycollate-elicited C3HeB/FeJ mouse peritoneal macrophages in vitro with subthreshold stimulatory concentrations of lipopolysaccharide (LPS) can induce hyporesponsiveness (desensitization) to both tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) production when these cells are subsequently stimulated with 100 ng/ml of LPS. We have established, however, that the primary dose of LPS required for inducing downregulation of NO production is significantly lower than that required for inducing downregulation of TNF-alpha production. Further, when LPS-pretreated macrophages become refractory to subsequent LPS stimulation for NO production, the secondary LPS-stimulated TNF-alpha production is markedly enhanced, and vice versa. These results indicate that LPS-induced TNF-alpha and NO production by macrophages are differentially regulated, and that the observed desensitization process may not reflect a state in which macrophages are totally refractory to subsequent LPS stimulation. Rather, our data suggest that LPS-pretreated macrophages become selectively primed for differential responses to LPS. The LPS-induced selective priming effects are not restricted to LPS stimulation, but extend as well to stimuli such as zymosan, Staphylococcus aureus, and heat-killed Listeria monocytogenes.

scholarly journals Innate Immunity to the Pathogenic Fungus Coccidioides posadasii Is Dependent on Toll-Like Receptor 2 and Dectin-1

2005 ◽  
Vol 73 (3) ◽  
pp. 1553-1560 ◽  
Author(s):  
Suganya Viriyakosol ◽  
Joshua Fierer ◽  
Gordon D. Brown ◽  
Theo N. Kirkland
Keyword(s):  
Cytokine Production ◽  
Pathogenic Fungus ◽  
Peritoneal Macrophages ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Coccidioides Posadasii ◽  
Necrosis Factor Alpha ◽  
Cytokine Responses ◽  
Factor Alpha ◽  
Mouse Peritoneal Macrophages

ABSTRACT Coccidioides posadasii is a pathogenic fungus that causes endemic and epidemic coccidioidomycosis in the deserts of North, Central, and South America. How the innate immune system responds to the organism is not well understood. Here we show that elicited mouse peritoneal macrophages respond to spherules (the tissue form of the fungus) by producing proinflammatory cytokines as measured by quantitative PCR of cellular transcripts and by enzyme-linked immunosorbent assay (ELISA) assays for secreted protein. We examined the contribution of Toll-like receptors (TLR) and MyD88 in macrophage responses to formalin-killed spherules (FKS) by comparing cytokine responses of elicited macrophages from different knockout mice. FKS were added to elicited mouse peritoneal macrophages from wild-type, TLR2−/−, and MyD88−/− cells, and wild-type cells made more tumor necrosis factor alpha, MIP-2, and interleukin 6 than did the mutant macrophages. In contrast, the C3H/HeJ mice, which have a point mutation in TLR4, and TLR4−/− B6 mice exhibited no defect in cytokine production compared to the control mice. We also investigated the role of the macrophage β-glucan receptor, Dectin-1. RAW 264.7 macrophages overexpressing Dectin-1 produced more cytokines in respond to FKS, live spherules, and purified β-glucan than did control RAW cells. Blockage of Dectin-1 with antibodies inhibited cytokine production in elicited mouse peritoneal macrophages. Taken together, these results show that cytokine responses in mouse peritoneal macrophages to C. posadasii spherules are dependent on TLR2, MyD88, and Dectin-1.

PCSK9 regulates expression of scavenger receptors and ox-LDL uptake in macrophages

2018 ◽  
Vol 114 (8) ◽  
pp. 1145-1153 ◽  
Author(s):  
Zufeng Ding ◽  
Shijie Liu ◽  
Xianwei Wang ◽  
Sue Theus ◽  
Xiaoyan Deng ◽  
...  
Keyword(s):  
Peritoneal Macrophages ◽  
Scavenger Receptors ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ldl Uptake ◽  
Factor Alpha ◽  
Pcsk9 Inhibition ◽  
Inflammatory Milieu ◽  
Mouse Peritoneal Macrophages ◽  
Necrosis Factor

Abstract Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to influence macrophage biology and modulate atherogenesis. We conducted this study to examine the regulation of scavenger receptors (SRs) (LOX-1, SRA, and CD36) and oxidized liporoptein cholesterol (ox-LDL) uptake in macrophages by PCSK9. Methods and results Treatment of mouse peritoneal macrophages with tumour necrosis factor alpha (TNF-α) resulted in concentration-dependent modest, but significant, increase in PCSK9 expression. Importantly, treatment of TNF-α primed macrophages with recombinant murine PCSK9 increased the expression of LOX-1, SRA, and CD36 2-5 fold, and enhanced ox-LDL uptake by ≈five-fold. The increase in LOX-1 was much greater than in SRA or CD36. PCSK9 inhibition (by siRNA transfection or use of macrophages from PCSK9−/− mice) reduced the expression of SRs (LOX-1 ≫ SRA or CD36). Ox-LDL uptake in response to PCSK9 was also inhibited in macrophages from LOX-1−/− mice (P < 0.05 vs. macrophages from SRA−/− and CD36−/− mice). Upregulation of PCSK9 by cDNA transfection induced intense ox-LDL uptake which was inhibited by co-transfection of cells with siRNA LOX-1 (P < 0.05 vs. siRNA SRA or siRNA CD36). Further, TNF-α-mediated PCSK9 upregulation and subsequent expression of SRs and ox-LDL uptake were reduced in macrophages from gp91phox−/−, p47phox−/− and p22phox−/− mice (vs. macrophages from wild-type mice). Conclusions This study shows that in an inflammatory milieu, elevated levels of PCSK9 potently stimulate the expression of SRs (principally LOX-1) and ox-LDL uptake in macrophages, and thus contribute to the process of atherogenesis.

Colchicine has opposite effects on interleukin-1 beta and tumor necrosis factor-alpha production

1991 ◽  
Vol 261 (4) ◽  
pp. L315-L321 ◽  
Author(s):  
J. N. Allen ◽  
D. J. Herzyk ◽  
M. D. Wewers
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cytokine Production ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

To study the role of microtubules in cytokine production, the effect of the microtubule depolymerizing agent colchicine on lipopolysaccharide endotoxin (LPS)-induced interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) release by blood monocytes and alveolar macrophages were examined. Immunofluorescence microscopy demonstrated that LPS resulted in the appearance of microtubule-containing cytoplasmic appendages and that colchicine, which resulted in microtubule disruption in monocytes, blocked appendage formation. Colchicine resulted in approximately 50% increase in LPS-induced IL-1 beta release and a 50% decrease in LPS-induced TNF-alpha release by human monocytes at all doses of LPS tested. Although colchicine resulted in a statistically significant increase in LPS-stimulated human alveolar macrophage IL-1 beta release, the increase was not as great as that observed with monocytes. Northern blot analysis suggested that the colchicine effect occurs pretranslationally because colchicine caused an increase in LPS-stimulated IL-1 beta mRNA levels and a decrease in TNF-alpha mRNA levels. These results suggest that microtubules contribute to the regulation of endotoxin-stimulated mononuclear phagocyte cytokine production and that this regulation differs significantly between IL-1 beta and TNF-alpha.

scholarly journals Erythromycin Inhibits Tumor Necrosis Factor Alpha and Interleukin 6 Production Induced by Heat-Killed Streptococcus pneumoniae in Whole Blood

1998 ◽  
Vol 42 (7) ◽  
pp. 1605-1609 ◽  
Author(s):  
Marc J. Schultz ◽  
Peter Speelman ◽  
Sebastian Zaat ◽  
Sander J. H. van Deventer ◽  
Tom van der Poll
Keyword(s):  
Streptococcus Pneumoniae ◽  
Tumor Necrosis Factor ◽  
Whole Blood ◽  
Tumor Necrosis ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT To determine the effects of penicillin and erythromycin on cytokine production induced by heat-killed Streptococcus pneumoniae (HKSP), we studied the effects of those drugs on cytokine production induced by S. pneumoniaein human whole blood in vitro and ex vivo. In whole blood in vitro, erythromycin, but not penicillin, caused a dose-dependent decrease in HKSP-induced production of tumor necrosis factor alpha (TNF) and interleukin 6 (IL-6), while the production of IL-10, IL-12, and gamma interferon was inhibited only at the highest erythromycin concentration tested (10−3 M). The production of TNF and IL-6 in whole blood obtained from healthy subjects after a 30-min infusion of erythromycin (1,000 mg) was lower after ex vivo stimulation with HKSP than that in blood drawn before the infusion. Inhibition of TNF contributed to erythromycin-induced inhibition of IL-6 synthesis. Inhibition of TNF and IL-6 production by erythromycin may have a negative impact on host defense mechanisms during pneumococcal pneumonia.

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