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Air Pouch (air + pouch)

Distribution by Scientific Domains

Medical Sciences	88%

Selected Abstracts

Induction of CCR2-dependent macrophage accumulation by oxidized phospholipids in the air-pouch model of inflammation

ARTHRITIS & RHEUMATISM, Issue 5 2009
Alexandra Kadl
Objective Macrophages are key players in the pathogenesis of rheumatoid synovitis as well as in atherosclerosis. To determine whether atherogenic oxidized phospholipids potentially contribute to synovial inflammation and subsequent monocyte/macrophage recruitment, we examined the effects of oxidized 1- palmitoyl-2-arachidonoyl- sn -3-glycero-phosphorylcholine (OxPAPC) on chemokine expression and leukocyte recruitment in a facsimile synovium in vivo using the murine air-pouch model. Methods Air pouches were raised by 2 injections of sterile air, and inflammation was induced by injecting either lipopolysaccharide (LPS) or OxPAPC into the pouch lumen. Inflammation was assessed by analysis of inflammatory gene expression using reverse transcription,polymerase chain reaction or immunohistochemical analysis, and leukocytes were quantified in the lavage fluid and in the pouch wall after staining with Giemsa or after enzymatic digestion followed by fluorescence-activated cell sorter analysis. Results Application of OxPAPC resulted in selective recruitment of monocyte/macrophages into the air-pouch wall, but not in the lumen. In contrast, LPS induced both monocyte and neutrophil accumulation in the pouch lumen as well as in the wall. LPS, but not OxPAPC, induced the expression of adhesion molecules E-selectin, P-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1. OxPAPC increased the expression of the CCR2 ligands monocyte chemotactic protein 1 (MCP-1), MCP-3, and MCP-5, as well as RANTES and growth-related oncogene , (GRO,), while it down-regulated the expression of CCR2 on macrophages. Moreover, oxidized phospholipid,induced macrophage accumulation was abrogated in CCR2,/, mice. Conclusion These data demonstrate that oxidized phospholipids trigger a type of inflammatory response that leads to selective macrophage accumulation in vivo, a process relevant for the pathogenesis of chronic inflammatory rheumatic diseases. [source]

The Anti-Inflammatory Effect of Bee Venom Stimulation in a Mouse Air Pouch Model Is Mediated by Adrenal Medullary Activity

JOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2003
Y.-B. Kwon
Abstract Cutaneous electrical or chemical stimulation can produce an anti-inflammatory effect, which is dependent on adrenal medullary-sympathetic activation. We have previously shown that peripheral injection of bee venom (BV) also produces a significant anti-inflammatory effect that is neurally mediated. In the present study, we examined whether this anti-inflammatory effect is also dependent on the adrenal gland using the mouse inflammatory air pouch model. Subcutaneous (s.c.) BV injection produced a marked suppression of leucocyte migration and tumour necrosis factor (TNF)- , concentration induced by zymosan injection into the air pouch. The role of the adrenal gland in this suppression was evaluated in adrenalectomized mice. Adrenalectomy significantly reversed the suppression of leucocyte migration and TNF- , elevation caused by BV. Serum concentrations of corticosteroid were increased in mice with zymosan-induced air-pouch inflammation and this increase was reduced by BV administration, suggesting that adrenal corticosteroid release is not involved in mediating the anti-inflammatory effects of BV. To test this hypothesis, the corticosteroid receptor antagonist (RU486) was administered and found not to affect the BV-induced inhibition of leucocyte migration. By contrast, pretreatment with the , -adrenergic antagonist propranolol reversed the BV-induced inhibitory effect on leucocyte migration. These results suggest that the anti-inflammatory effect of s.c. BV administration is mediated in part by the release of catecholamines from the adrenal medulla. [source]

The anti-inflammatory modulatory role of Solidago chilensis Meyen in the murine model of the air pouch

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2008
Rafael Liz
The aim of this study was to investigate the anti-inflammatory efficacy of an aqueous extract (AE), and its butanolic (BuOH) and aqueous residual (AR) fractions, derived from the rhizome of Solidago chilensis in inflammation caused by carrageenan in mice. Solidago chilensis Meyen rhizome was extracted using hot water at 90°C under infusion. The extract was filtered and lyophilized. Part of the aqueous extract was fractionated with n-BuOH, resulting in butanolic (BuOH) and aqueous residual (AR) fractions. Adult Swiss mice were used in the in-vivo experiments. We evaluated the effect of rhizome aqueous extract of Solidago chilensis and these two derived fractions on the inflammation induced by carrageenan in the mouse model of the air pouch. The aqueous extract and its derived fractions significantly inhibited leucocytes, neutrophils, exudation, myeloperoxidase and adenosine deaminase activity, as well as nitric oxide, interleukin-1 beta (IL-1,), neutrophil chemokine (KC) and tumour necrosis factor-alpha (TNF-,) levels (P < 0.05). Indometacin and dexamethasone inhibited all the studied inflammatory parameters (P < 0.01) with the exceptions that indometacin did not inhibit TNF-, levels and dexamethasone did not inhibit KC levels (P > 0.05). These results indicate that Solidago chilensis has a significant anti-inflammatory action on acute inflammatory responses and that its inhibitory activity may be due not only to the inhibition of pro-inflammatory mediators, but also to the inhibition of leucocyte infiltration. [source]

Role of the leucine-rich repeat domain of cryopyrin/NALP3 in monosodium urate crystal,induced inflammation in mice

ARTHRITIS & RHEUMATISM, Issue 7 2010
Hal M. Hoffman
Objective The mechanism by which monosodium urate monohydrate (MSU) crystals intracellularly activate the cryopyrin inflammasome is unknown. The aim of this study was to use a mouse molecular genetics,based approach to test whether the leucine-rich repeat (LRR) domain of cryopyrin is required for MSU crystal,induced inflammation. Methods Cryopyrin-knockout lacZ (Cryo,Z/,Z) mice and mice with the cryopyrin LRR domain deleted and fused to the lacZ reporter (Cryo,LRR Z/,LRR Z) were generated using bacterial artificial chromosome,based targeting vectors, which allow for large genomic deletions. Bone marrow,derived macrophages from Cryo,LRR Z/,LRR Z mice, Cryo,Z/,Z mice, and congenic wild-type (WT) mice were challenged with endotoxin-free MSU crystals under serum-free conditions. Phagocytosis and cytokine expression were assessed by flow cytometry and enzyme-linked immunosorbent assay. MSU crystals also were injected into mouse synovial-like subcutaneous air pouches. The in vivo inflammatory responses were examined. Results Release of interleukin-1, (IL-1,), but not CXCL1 and tumor necrosis factor ,, was impaired in Cryo,LRR Z/,LRR Z and Cryo,Z/,Z mouse bone marrow,derived macrophages compared with WT mouse bone marrow,derived macrophages in response to not only MSU crystals but also other known stimuli that activate the cryopyrin inflammasome. In addition, a comparable percentage of MSU crystals taken up by each type of bone marrow,derived macrophage was observed. Moreover, total leukocyte infiltration in the air pouch and IL-1, production were attenuated in Cryo,Z/,Z and Cryo,LRR Z/,LRR Z mice at 6 hours postinjection of MSU crystals compared with WT mice. Conclusion MSU crystal,induced inflammatory responses were comparably attenuated both in vitro and in vivo in Cryo,LRR Z/,LRR Z and Cryo,Z/,Z mice. Hence, the LRR domain of cryopyrin plays a role in mediating MSU crystal,induced inflammation in this model. [source]

Inhibitory effect of the coffee diterpene kahweol on carrageenan-induced inflammation in rats

BIOFACTORS, Issue 1 2006
Ji Young Kim
Abstract Previous studies reported that kahweol, a coffee-specific diterpene, inhibits cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in cultured lipopolysaccharide-activated macrophages. The aim of this study was to confirm the anti-inflammatory effects of kahweol by examining its effect on the inflammatory response induced by carrageenan in a rat using an acute air pouch inflammation model. Kahweol significantly reduced the levels of the inflammatory process markers in the air pouch, such as the volume of exudates, the amount of protein and the number of leukocytes and neutrophils. The levels of nitrite, TNF-a and prostaglandin E2 (PGE2) were also markedly lower in the air pouch of the kahweol-treated animals than in the controls. Immunoblot analysis showed that kahweol reduced the COX-2 and iNOS expression level in the exudate cells. The histological examination showed that there was a lower inflammatory response in the pouch tissues from the kahweol-treated animals. In addition, kahweol significantly reduced the paw edema induced by carrageenan and also markedly reduced the level of PGE2 production in the inflamed paw. These results suggest that kahweol has significant anti-inflammatory effects in vivo, which might be due to the inhibition of iNOS and COX-2 expression in the inflammatory sites. [source]

Preclinical pharmacology of robenacoxib: a novel selective inhibitor of cyclooxygenase-2

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009
J. N. KING
This manuscript reports the results of preclinical studies in the rat with robenacoxib, a novel selective cyclooxygenase (COX)-2 inhibitor. Robenacoxib selectively inhibited COX-2 in vitro as evidenced from COX-1:COX-2 IC50 ratios of 27:1 in purified enzyme preparations and >967:1 in isolated cell assays. Binding to COX-1 was rapid and readily reversible (dissociation t1/2 << 1 min), whilst COX-2 binding was slowly reversible (t1/2 = 25 min). In vivo, robenacoxib inhibited PGE2 production (an index of COX-2 inhibition) in lipopolysaccharide (LPS)-stimulated air pouches (ID50 0.3 mg/kg) and for at least 24 h in zymosan-induced inflammatory exudate (at 2 mg/kg). Robenacoxib was COX-1 sparing, as it inhibited serum TxB2 synthesis ex vivo (an index of COX-1 inhibition) only at very high doses (100 mg/kg but not at 2,30 mg/kg). Robenacoxib inhibited carrageenan-induced paw oedema (ID50 0.40,0.48 mg/kg), LPS-induced fever (ID50 1.1 mg/kg) and Randall,Selitto pain (10 mg/kg). Robenacoxib was highly bound to plasma protein (99.9% at 50 ng/mL in vitro). After intravenous dosing, clearance was 2.4 mL/min/kg and volume of distribution at steady-state was 306 mL/kg. Robenacoxib was preferentially distributed into inflammatory exudate; the AUC for exudate was 2.9 times higher than for blood and the MRT in exudate (15.9 h) was three times longer than in blood (5.3 h). Robenacoxib produced significantly less gastric ulceration and intestinal permeability as compared with the reference nonsteroidal anti-inflammatory drug (NSAID), diclofenac, and did not inhibit PGE2 or 6-keto PGF1, concentrations in the stomach and ileum at 30 mg/kg. Robenacoxib also had no relevant effects on kidney function at 30 mg/kg. In summary, results of preclinical studies in rats studies suggest that robenacoxib has an attractive pharmacological profile for potential use in the intended target species, cats and dogs. [source]

Role of the leucine-rich repeat domain of cryopyrin/NALP3 in monosodium urate crystal,induced inflammation in mice

The critical role of kinase activity of interleukin-1 receptor,associated kinase 4 in animal models of joint inflammation

ARTHRITIS & RHEUMATISM, Issue 6 2009
Magdalena Koziczak-Holbro
Objective We have previously reported that the kinase activity of interleukin-1 receptor,associated kinase 4 (IRAK-4) is important for Toll-like receptor and interleukin-1 receptor signaling in vitro. Using mice devoid of IRAK-4 kinase activity (IRAK-4 KD mice), we undertook this study to determine the importance of IRAK-4 kinase function in complex disease models of joint inflammation. Methods IRAK-4 KD mice were subjected to serum transfer,induced (K/BxN) arthritis, and migration of transferred spleen lymphocytes into joints and cartilage and bone degradation were assessed. T cell response in vivo was tested in antigen-induced arthritis (AIA) by measuring the T cell,dependent antigen-specific IgG production and frequency of antigen-specific T cells in the spleen and lymph nodes. T cell allogeneic response was tested in vitro by mixed lymphocyte reaction (MLR). Results Lipopolysaccharide-induced local neutrophil influx into subcutaneous air pouches was impaired in IRAK-4 KD mice. These mice were also protected from inflammation in the K/BxN and AIA models, as shown by reduced swelling of joints. Histologic analysis of joints of K/BxN serum,injected mice revealed that bone erosion, osteoclast formation, and cartilage matrix proteoglycan loss were reduced in IRAK-4 KD mice. Assessment of T cell response by MLR, by frequency of antigen-specific clones, and by production of antigen-specific IgG did not reveal substantial differences between IRAK-4 KD and wild-type mice. Conclusion These results demonstrate that IRAK-4 is a key component for the development of proarthritis inflammation, but that it is not crucial for T cell activation. Therefore, the kinase function of IRAK-4 appears to be an attractive therapeutic target in chronic inflammation. [source]