scholarly journals Mycoplasma pneumoniae-Derived Lipopeptides Induce Acute Inflammatory Responses in the Lungs of Mice

2007 ◽  
Vol 76 (1) ◽  
pp. 270-277 ◽  
Author(s):  
Takashi Shimizu ◽  
Yutaka Kida ◽  
Koichi Kuwano
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Peritoneal Macrophages ◽  
Necrosis Factor Alpha ◽  
Chemokine Production ◽  
Cytokines And Chemokines ◽  
Tnf Α ◽  
Mouse Peritoneal Macrophages

ABSTRACT The pathogenesis of Mycoplasma pneumoniae infection is considered to be in part attributable to excessive immune responses. In this study, we investigated whether synthetic lipopeptides of subunit b of F0F1-type ATPase (F0F1-ATPase), NF-κB-activating lipoprotein 1 (N-ALP1), and N-ALP2 (named FAM20, sN-ALP1, and sN-ALP2, respectively) derived from M. pneumoniae induce cytokine and chemokine production and leukocyte infiltration in vivo. Intranasal administration of FAM20 and sN-ALP2 induced infiltration of leukocyte cells and production of chemokines and cytokines in bronchoalveolar lavage fluid, but sN-ALP1 failed to do so. The activity of FAM20 was notably higher than that of sN-ALP2. FAM20 and sN-ALP2 induced tumor necrosis factor alpha (TNF-α) through Toll-like receptor 2 in mouse peritoneal macrophages. Moreover, in the range of low concentrations of lipopeptides, FAM20 showed relatively high activity of inducing TNF-α in mouse peritoneal macrophages compared to synthetic lipopeptides such as MALP-2 and FSL-1, derived from Mycoplasma fermentans and Mycoplasma salivarium, respectively. These findings indicate that the F0F1-ATPase might be a key molecule in inducing cytokines and chemokines contributing to inflammatory responses during M. pneumoniae infection in vivo.

scholarly journals Mechanisms Involved in the Pathogenesis of Sepsis Are Not Necessarily Reflected by In Vitro Cell Activation Studies

1998 ◽  
Vol 66 (11) ◽  
pp. 5372-5378 ◽  
Author(s):  
Claudia R. Amura ◽  
R. Silverstein ◽  
D. C. Morrison
Keyword(s):  
Cell Activation ◽  
Endotoxic Shock ◽  
Peritoneal Macrophages ◽  
In Vitro Studies ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
In Vitro Systems ◽  
A Cell

ABSTRACT It is thought that lipopolysaccharide (LPS) from gram-negative bacteria contributes significantly to the pathogenesis of septic shock. In vitro studies to address the mechanisms involved in this process have often investigated human monocytes or mouse macrophages, since these cells produce many of the mediators found in septic patients. Targeting of these mediators, especially tumor necrosis factor alpha (TNF-α), has been pursued as a means of reducing mortality in sepsis. Two experimental approaches were designed to test the assumption that in vitro studies with macrophages accurately predict in vivo mechanisms of LPS pathogenesis. In the first approach, advantage was taken of the fact that on consecutive days after injection of thioglycolate into mice, increased numbers of macrophages could be harvested from the peritoneum. These cells manifested markedly enhanced levels of in vitro TNF-α, interleukin 6 (IL-6), and nitric oxide production in response to LPS. In d-galactosamine-sensitized mice, however, thioglycolate treatment significantly decreased mortality due to LPS, as well as levels of circulating TNF-α and IL-6. Anti-TNF-α treatment confirmed this cytokine’s role in the observed lethality. In a second experimental approach, we compared the mouse macrophage-stimulating potencies of different LPS preparations with their lethalities to mice. In these studies, the in vitro macrophage-stimulating profiles presented by rough-LPS and smooth-LPS preparations were the reverse of their relative lethal potencies in vivo. In conclusion, peritoneal macrophages appear not to be the major cells responsible for the overall host response during endotoxic shock. These findings underscore the importance of verifying the correlation of in vivo systems with in vitro systems when attributing specific functions to a cell type.

scholarly journals Heat-killed Tsukamurella inchonensis reduces lipopolysaccharide-induced inflammatory responses in activated murine peritoneal macrophages

2017 ◽  
Vol 62 (No. 12) ◽  
pp. 668-673 ◽  
Author(s):  
K. Nofouzi ◽  
M. Aghapour ◽  
B. Baradaran ◽  
GH Hamidian ◽  
P. Zare ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Peritoneal Macrophages ◽  
Interferon Γ ◽  
No Production ◽  
Griess Reaction ◽  
Indirect Technique ◽  
Factor Α ◽  
Mouse Peritoneal Macrophages

Tsukamurella inchonensis (T. inchonensis) is an aerobic species of Actinomycetales which has immunomodulatory activities when used as a suspension of killed bacilli. Here, the effects of T. inchonensis on lipopolysaccharide-induced inflammatory responses in mouse peritoneal macrophages have been examined. Peritoneal macrophages were harvested by lavaging with ice cold phosphate-buffered saline. Macrophages acquired from mice treated with different doses of T. inchonensis for seven days were cultured with 20 U/ml interferon-γ and 10 µg/ml lipopolysaccharide for in vivo assays. Nitrite levels were measured by using the diazotization method based on the Griess reaction, an indirect technique to determine nitric oxide (NO) production. T. inchonensis inhibited lipopolysaccharide-stimulated NO production in mouse peritoneal macrophages from mice previously exposed to concentrations of 108 and 5 × 10<sup>7</sup> CFU per flask. Also, T. inchonensis decreased lipopolysaccharide-induced production of pro-inflammatory cytokines, including interleukin-6 and tumor necrosis factor-α. Thus, it can be concluded that T. inchonensis is a powerful inhibitor of lipopolysaccharide-induced NO production in activated murine macrophages, and T. inchonensis may be useful as a novel agent for chemoprevention in inflammatory diseases.

scholarly journals Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo

Blood ◽  
2002 ◽  
Vol 99 (3) ◽  
pp. 1053-1059 ◽  
Author(s):  
Frank M. Szaba ◽  
Stephen T. Smiley
Keyword(s):  
Inflammatory Responses ◽  
Direct Injection ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Chemokine Production ◽  
Monocyte Chemoattractant Protein 1 ◽  
Macrophage Adhesion ◽  
Pleiotropic Functions ◽  
Deficient Mice

Abstract Extravascular coagulation leading to fibrin deposition accompanies many immune and inflammatory responses. Although recognized by pathologists for decades, and probably pathologic under certain conditions, the physiologic functions of extravascular coagulation remain to be fully defined. This study demonstrates that thrombin can activate macrophage adhesion and prompt interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) production in vivo. Peritoneal macrophages were elicited with thioglycollate (TG) and then activated in situ, either by intraperitoneal injection of lipopolysaccharide (LPS) or by injection of antigen into mice bearing antigen-primed T cells. Others previously established that such treatments stimulate macrophage adhesion to the mesothelial lining of the peritoneal cavity. The present study demonstrates that thrombin functions in this process, as macrophage adhesion was suppressed by Refludan, a highly specific thrombin antagonist, and induced by direct peritoneal administration of purified thrombin. Although recent studies established that protease activated receptor 1 (PAR-1) mediates some of thrombin's proinflammatory activities macrophage adhesion occurred normally in PAR-1–deficient mice. However, adhesion was suppressed in fibrin(ogen)-deficient mice, suggesting that fibrin formation stimulates macrophage adhesion in vivo. This study also suggests that fibrin regulates chemokine/cytokine production in vivo, as direct injection of thrombin stimulated peritoneal accumulation of IL-6 and MCP-1 in a fibrin(ogen)-dependent manner. Given that prior studies have clearly established inflammatory roles for PAR-1, thrombin probably has pleiotropic functions during inflammation, stimulating vasodilation and mast cell degranulation via PAR-1, and activating cytokine/chemokine production and macrophage adhesion via fibrin(ogen).

Eucommiae Cortex Inhibits TNF-α and IL-6 Through the Suppression of Caspase-1 in Lipopolysaccharide-Stimulated Mouse Peritoneal Macrophages

2012 ◽  
Vol 40 (01) ◽  
pp. 135-149 ◽  
Author(s):  
Min-Cheol Kim ◽  
Dae-Seung Kim ◽  
Su-Jin Kim ◽  
Jinbong Park ◽  
Hye-Lin Kim ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Pharmacological Action ◽  
Underlying Mechanism ◽  
Peritoneal Macrophages ◽  
Prostaglandin E ◽  
Necrosis Factor Alpha ◽  
Caspase 1 ◽  
Factor Alpha ◽  
Mouse Peritoneal Macrophages

Eucommiae cortex (EC) is used in various traditional Korean medicines in the form of tonics, analgesics, and sedatives. However, the underlying mechanism of its anti-inflammatory effect remains unclear. This study attempts to determine the effects of EC on lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. The findings of the study show that EC inhibits the LPS-induced production of tumor necrosis factor-alpha and interleukin-6. Exposure to EC also reduces an inflammation-induced increase in the levels of cyclooxigenase-2 and the production of prostaglandin E 2 and nitric oxide in mouse peritoneal macrophages. Furthermore, EC suppresses the activation of nuclear factor-kappa B and caspase-1. These results provide novel insights into the pharmacological action of EC and indicate that EC has a potential in the treatment of inflammatory diseases.

Studies on cytokine activation of listericidal activity in murine macrophages

1990 ◽  
Vol 36 (10) ◽  
pp. 671-675 ◽  
Author(s):  
Michel Denis ◽  
Evan O. Gregg
Keyword(s):  
Peritoneal Macrophages ◽  
Interferon Γ ◽  
Necrosis Factor Alpha ◽  
Cytokine Activation ◽  
Inhibition Of Growth ◽  
Cytokine Treatment ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ

The ability of a variety of soluble factors, alone or in combination, to endow murine resident peritoneal macrophages with listericidal activity was assessed. Inhibition of growth and (or) killing of Listeria in infected macrophages was determined by the uptake of [3H]uracil following lysis of the infected macrophage monolayers. Interferon-γ was shown to induce modest listericidal activity in murine resident macrophages as compared with untreated monolayers. Treatment with tumour necrosis factor alpha also induced significant listericidal activity in this system. Among other cytokines tested, IL-4 induced an ability to inhibit growth of Listeria in resident macrophages. The ability of cytokines to act in an additive or synergistic fashion with IFN-γ was also investigated. Combinations of IFN-γ and IL-4 and IFN-γ and IL-2 induced listericidal activity not greater than that seen with IFN-γ alone. IFN-γ and TNF-α were shown to increase bactericidal activity in an additive fashion. However, elicited macrophages were shown to spontaneously exert a significant listericidal activity that was not enhanced by cytokine treatment. Collectively, these findings show that cytokine treatment induced rather modest enhancement in listericidal activity in murine resident peritoneal macrophages and no enhancement whatsoever in elicited macrophages. Thus, in in vivo situations where Listeria organisms are completely cleared from the infected organs, mechanisms other than lymphokine-induced listericidal activity of resident macrophages would seem to be operating. Key words: Listeria, macrophages, cytokines.

scholarly journals Chemokine C10 Promotes Disease Resolution and Survival in an Experimental Model of Bacterial Sepsis

2000 ◽  
Vol 68 (11) ◽  
pp. 6108-6114 ◽  
Author(s):  
M. L. Steinhauser ◽  
C. M. Hogaboam ◽  
A. Matsukawa ◽  
N. W. Lukacs ◽  
R. M. Strieter ◽  
...  
Keyword(s):  
Host Defense ◽  
Cecal Ligation ◽  
Peritoneal Macrophages ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Septic Peritonitis

ABSTRACT Previous studies have suggested that the C-C chemokine C10 is involved in the chronic stages of host defense reactions. The present study addressed the role of C10 in a murine model of septic peritonitis, induced by cecal ligation and puncture (CLP). Unlike other C-C chemokines, C10 levels in the peritoneal wash were increased approximately 30-fold above baseline levels at 48 h after CLP surgery. Immunoneutralization of peritoneal C10 levels with polyclonal anti-C10 antiserum during CLP-induced peritonitis negatively impacted mouse survival over 4 days. In contrast, when 500 ng of recombinant murine C10 was administered immediately after CLP surgery, the 4-day survival rate increased from 20% to over 60%. The C10 therapy appeared to facilitate a rapid and significant enhancement of the levels of tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) and a later increase in interleukin-13 (IL-13) levels in the peritoneal cavity. In vitro studies showed that the combination of IL-1β and C10 markedly augmented TNF-α synthesis by peritoneal macrophages and that C10 synthesis was induced in these cells following their exposure to IL-13. At 24 h after CLP surgery, only 25% of C10-treated mice were bacteremic versus 85% of the control group that exhibited dissemination of bacteria into the circulation. The lack of bacteremia in C10-treated mice appeared to be related, in part, to in vitro evidence that C10 significantly enhanced the bacterial phagocytic activity of peritoneal macrophages. In addition, in vivo evidence suggested that C10 therapy significantly reduced the amount of material that leaked from the damaged gut. Taken together, the results of this study demonstrate that the C10 chemokine rapidly promotes disease resolution in the CLP model through its direct effects on the cellular events critically involved in host defense during septic peritonitis.

scholarly journals Cytokine Profiling of Macrophages Exposed to Porphyromonas gingivalis, Its Lipopolysaccharide, or Its FimA Protein

2005 ◽  
Vol 73 (2) ◽  
pp. 935-943 ◽  
Author(s):  
Qingde Zhou ◽  
Tesfahun Desta ◽  
Matthew Fenton ◽  
Dana T. Graves ◽  
Salomon Amar
Keyword(s):  
Porphyromonas Gingivalis ◽  
Peritoneal Macrophages ◽  
Cytokine Profile ◽  
Enzyme Linked Immunosorbent Assay ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Antibody Arrays ◽  
Mouse Peritoneal Macrophages

ABSTRACT To characterize the roles of Porphyromonas gingivalis and its components in the disease processes, we investigated the cytokine profile induced by live P. gingivalis, its lipopolysaccharides (LPS), and its major fimbrial protein, fimbrillin (FimA). Using cytokine antibody arrays, we found that P. gingivalis LPS and FimA induced a similar profile of cytokine expression when exposed to mouse peritoneal macrophages but that this profile differed significantly in response to live P. gingivalis. In vitro, mouse peritoneal macrophages were stimulated to produce interleukin-6 (IL-6), granulocyte colony-stimulating factor, and lymphotactin by live P. gingivalis, but not by P. gingivalis LPS or FimA, while RANTES, gamma interferon, IL-17, vascular cell adhesion molecule 1 (VCAM-1), and vascular endothelial growth factor were induced by P. gingivalis LPS or FimA, but not by live P. gingivalis. In vivo, IL-6 mRNA was strongly induced only by live P. gingivalis while monocyte chemoattractant protein 1 mRNA was strongly induced only by P. gingivalis LPS and FimA in mouse calvarial scalp, further confirming the differences of cytokine profile induced in vitro. Cytokine antibody arrays using toll-like receptor 2 (TLR2)- and TLR4-deficient macrophages revealed that most of the cytokines induced by P. gingivalis LPS or FimA signal through TLR2, while most of cytokines induced by live P. gingivalis signal through both TLR2 and TLR4. Interestingly, the activation of TLR2 by live P. gingivalis inhibited the release of RANTES, VCAM-1, and IL-1α from mouse peritoneal macrophages. A tumor necrosis factor alpha enzyme-linked immunosorbent assay further confirmed that P. gingivalis LPS and FimA activate mouse peritoneal macrophages via TLR2. These results indicate that host immune cells sense live P. gingivalis and its components differently, which translates into the expression of different inflammatory cytokine profiles.

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 &lt; 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 &lt; 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.

scholarly journals Tigecycline Therapy Significantly Reduces the Concentrations of Inflammatory Pulmonary Cytokines and Chemokines in a Murine Model of Mycoplasma pneumoniae Pneumonia

2009 ◽  
Vol 53 (4) ◽  
pp. 1546-1551 ◽  
Author(s):  
C. M. Salvatore ◽  
C. Techasaensiri ◽  
C. Tagliabue ◽  
K. Katz ◽  
N. Leos ◽  
...  
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Murine Model ◽  
Statistical Significance ◽  
Community Acquired Pneumonia ◽  
Necrosis Factor Alpha ◽  
Cytokines And Chemokines ◽  
Tnf Α ◽  
Wide Range ◽  
Ifn Γ

ABSTRACT Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecycline belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of microorganisms, including in vitro activity against M. pneumoniae. We investigated the effect of tigecycline on microbiologic, histologic, and immunologic indices in a murine model of M. pneumoniae pneumonia. BALB/c mice were inoculated intranasally with M. pneumoniae and treated subcutaneously with tigecycline or placebo for 6 days. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine and chemokine concentrations (tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], interleukin 1β [IL-1β], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1α, MIG, KC, MCP-1, and IP-10). BAL M. pneumoniae concentrations in mice treated with tigecycline (MpTige) tended to be reduced compared with mice treated with placebo (MpPl); however this did not reach statistical significance. The lung HPS was significantly lower, as well as the parenchymal-pneumonia subscore, in the MpTige mice than in the MpPl mice. MpTige mice had significantly lower BAL cytokine concentrations of IL-1β, IL-12 (p40/p70), IFN-γ, and TNF-α; of the chemokines, MIG, MIP-1α, and IP-10 were statistically lower in MpTige mice. While tigecycline treatment demonstrated a modest microbiologic effect, it significantly improved lung histologic inflammation and reduced pulmonary cytokines and chemokines.

Sign in / Sign up

Export Citation Format

Share Document