IL-6 In Peritoneal Macrophages Research Articles

A homogalacturonan from Hippophae rhamnoides L. Berries enhance immunomodulatory activity through TLR4/MyD88 pathway mediated activation of macrophages

Our previous study isolated a natural high-methoxyl homogalacturonan (HRWP-A) from Hippophae rhamnoides and showed antitumor activity in vivo. In this study, the immunomodulatory activity and mechanisms of action of HRWP-A were further investigated. Results showed that HRWP-A could recover the body condition and activated macrophage in Cyclophosphamide (CTX)-induced immunosuppressed mice. Further, we investigated the possible mechanism underlying the effects of HRWP-A on mouse peritoneal macrophages. qPCR and western blot revealed that HRWP-A upregulated the expression of TLR4 mRNA in vitro. This process was accompanied by a clear increase in MyD88 expression and p-IκB-α, but these effects were largely abrogated by pretreatment with anti-TLR4 antibodies. The effects of HRWP-A on macrophage NO, IL-1β and IL-6 production were also inhibited by anti-TLR4 antibodies and were greatly influenced by the NF-κB inhibitor PDTC. Moreover, HRWP-A failed to induce the production of NO, IL-1β and IL-6 in peritoneal macrophages prepared from C3H/HeJ mice, which have a point mutation in the Tlr4 gene, suggesting the involvement of the TLR4 molecule in HRWP-A-mediated macrophage activation. These results may have important implications for our understanding of the structure-activity relationship of immunopotentiating polysaccharides from medicinal herbs.

Myeloid Cell Prostaglandin E2 Receptor EP4 Modulates Cytokine Production but Not Atherogenesis in a Mouse Model of Type 1 Diabetes.

Type 1 diabetes mellitus (T1DM) is associated with cardiovascular complications induced by atherosclerosis. Prostaglandin E2 (PGE2) is often raised in states of inflammation, including diabetes, and regulates inflammatory processes. In myeloid cells, a key cell type in atherosclerosis, PGE2 acts predominately through its Prostaglandin E Receptor 4 (EP4; Ptger4) to modulate inflammation. The effect of PGE2-mediated EP4 signaling specifically in myeloid cells on atherosclerosis in the presence and absence of diabetes is unknown. Because diabetes promotes atherosclerosis through increased arterial myeloid cell accumulation, we generated a myeloid cell-targeted EP4-deficient mouse model (EP4M-/-) of T1DM-accelerated atherogenesis to investigate the relationship between myeloid cell EP4, inflammatory phenotypes of myeloid cells, and atherogenesis. Diabetic mice exhibited elevated plasma PGE metabolite levels and elevated Ptger4 mRNA in macrophages, as compared with non-diabetic littermates. PGE2 increased Il6, Il1b, Il23 and Ccr7 mRNA while reducing Tnfa mRNA through EP4 in isolated myeloid cells. Consistently, the stimulatory effect of diabetes on peritoneal macrophage Il6 was mediated by PGE2-EP4, while PGE2-EP4 suppressed the effect of diabetes on Tnfa in these cells. In addition, diabetes exerted effects independent of myeloid cell EP4, including a reduction in macrophage Ccr7 levels and increased early atherogenesis characterized by relative lesional macrophage accumulation. These studies suggest that this mouse model of T1DM is associated with increased myeloid cell PGE2-EP4 signaling, which is required for the stimulatory effect of diabetes on IL-6, markedly blunts the effect of diabetes on TNF-α and does not modulate diabetes-accelerated atherogenesis.

Effect of bengkoang (Pachyrhizus erosus) fiber extract on murine macrophage-like J774.1 cells and mouse peritoneal macrophages

Bengkoang (Pachyrhizus erosus (L) Urban) is an edible root vegetable containing fairly large amounts of carbohydrates and crude fibers. The purpose of this study is to evaluate the effects of the bengkoang fiber extract (BFE) on macrophages in vitro and in vivo. BEF was prepared by heat-extraction from the bengkoang fiber in distilled water at 121°C for 20min. BFE stimulated the phagocytotic activity of J774.1 cells. In addition, BFE significantly facilitated production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 by J774.1 cells and mouse peritoneal macrophages. BFE also facilitated the gene expression levels of inducible nitric oxide synthase and cyclooxygenase-2. The phagocytotic activity of mouse peritoneal macrophages was significantly enhanced by oral administration of BFE to BALB/c mice for 7days. Ex vivo analysis revealed that production and gene expression of TNF-α and IL-6 in peritoneal macrophages from the BFE-administered mice were significantly enhanced. These results demonstrated that BFE activates macrophages in vitro and in vivo.

Effects of Oat β-Glucan on the Macrophage Cytokine Response to Herpes Simplex Virus 1 InfectionIn Vitro

Oat β-glucan can counteract the increased risk for Herpes Simplex Virus 1 (HSV-1) infection in mice, the effects of which have, at least in part, been attributed to macrophages. However, the specific responses of macrophages to oat β-glucan treatment in this model have yet to be elucidated. We examined the effects of varying doses of oat β-glucan on the pro-inflammatory cytokine response in both peritoneal and lung macrophages with and without exposure to HSV-1 infection in vitro. Peritoneal and lung macrophages were obtained from mice and cultured with varying concentrations of oat β-glucan (0 (control), 10, 100, and 1,000 μg) for 24 h and supernatants were collected. A standardized dose of HSV-1 was added for a second 24 h incubation period after which supernatants were again collected. Samples were analyzed for interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α) using enzyme linked immunosorbent assay (ELISA). In most cases, oat β-glucan resulted in a dose-dependent increase in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in lung and peritoneal macrophages with and without exposure to HSV-1 infection. When comparing across macrophage source, this response was greater for IL-1β and IL-6 in peritoneal macrophages and for TNF-α in lung macrophages. This may be a mechanism for the decreased risk for HSV-1 infection following oat β-glucan feedings in mice.

Myrrh Inhibits LPS-Induced Inflammatory Response and Protects from Cecal Ligation and Puncture-Induced Sepsis

Myrrh has been used as an antibacterial and anti-inflammatory agent. However, effect of myrrh on peritoneal macrophages and clinically relevant models of septic shock, such as cecal ligation and puncture (CLP), is not well understood. Here, we investigated the inhibitory effect and mechanism(s) of myrrh on inflammatory responses. Myrrh inhibited LPS-induced productions of inflammatory mediators such as nitric oxide, prostaglandin E2, and tumor necrosis factor-α but not of interleukin (IL)-1β and IL-6 in peritoneal macrophages. In addition, Myrrh inhibited LPS-induced activation of c-jun NH2-terminal kinase (JNK) but not of extracellular signal-regulated kinase (ERK), p38, and nuclear factor-κB. Administration of Myrrh reduced the CLP-induced mortality and bacterial counts and inhibited inflammatory mediators. Furthermore, administration of Myrrh attenuated CLP-induced liver damages, which were mainly evidenced by decreased infiltration of leukocytes and aspartate aminotransferase/alanine aminotransferase level. Taken together, these results provide the evidence for the anti-inflammatory and antibacterial potential of Myrrh in sepsis.

Reduced synthesis of inflammatory cytokines by a free radical scavenger after hemorrhagic shock in rats

Intestinal ischemia/reperfusion during hemorrhage and resuscitation may be a major trigger for cytokine expression. To assess whether free radicals produced on tissue reperfusion may play a role in the inflammatory response after hemorrhage, we tested the effect of a free radical scavenger on the production of inflammatory cytokines in a rat model of hemorrhagic shock. A prospective, controlled animal study. A university research laboratory. Male Wistar rats. Hemorrhage was induced in anesthetized rats. by bleeding the animal to achieve a mean arterial blood pressure of 40 mm Hg for 60 mins. Resuscitation was then induced by reinjecting shed blood followed by NaCl 0.9% to maintain arterial blood pressure within control values. Treated rats received the free radical scavenger N-2-mercaptopropionyl glycine (MPG; 20mg/kg iv bolus 30 mins before resuscitation followed by 20 mg/kg/hr). MPG reduced the volume of saline necessary to restore blood pressure during resuscitation (untreated 85+/-6; MPG 35+/-5 mL/kg; p < .05). As compared with untreated rats, MPG markedly reduced the systemic and mesenteric plasma concentrations of tumor necrosis factor (TNF)-alpha (as measured by ELISA) and interleukin (IL)-6 (as measured by bioassay), assessed at the end of resuscitation. MPG also reduced TNF-alpha and IL-6 mRNA expression (as measured by reverse transcriptase-polymerase chain reaction) assessed in peritoneal macrophages isolated from shock rats. Finally, in vitro experiments showed that MPG also markedly reduced the mRNA expression and release of TNF-alpha and IL-6 in peritoneal macrophages isolated from normal rats and subjected to hypoxia and reoxygenation. Reactive oxygen species contribute to the production of proinflammatory cytokines during posthemorrhage resuscitation. Free radicals scavengers may be a useful treatment in the prevention of the systemic inflammatory response that occurs in shock states.

Prevention of endotoxin-induced lethality in mice by calmodulin kinase activator.

Porphyromonas gingivalis strain 381 lipid A showed lower activity in inducing interleukin (IL)-1alpha and IL-1beta production and cytokine mRNA expression than synthetic Escherichia coli lipid A (compound 506) in alveolar macrophages of C57BL/6 mice. Both the lipid As induced tumor necrosis factor alpha in alveolar macrophages and IL-6 in peritoneal macrophages. A calmodulin (CaM) antagonist, W-7, inhibited IL-1beta production and its mRNA expression induced by P. gingivalis lipid A but not compound 506 in alveolar macrophages. A CaM kinase activator reduced the induction of IL-1beta in the serum of mice when administered with compound 506, and protected the mice against the lethal toxicity. The modulation of a variety of intracellular enzymes including the CaM kinase may result in clinical control of endotoxic sepsis.

Prevention of endotoxin-induced lethality in mice by calmodulin kinase activator

Porphyromonas gingivalis strain 381 lipid A showed lower activity in inducing interleukin (IL)-1α and IL-1β production and cytokine mRNA expression than synthetic Escherichia coli lipid A (compound 506) in alveolar macrophages of C57BL/6 mice. Both the lipid As induced tumor necrosis factor α in alveolar macrophages and IL-6 in peritoneal macrophages. A calmodulin (CaM) antagonist, W-7, inhibited IL-1β production and its mRNA expression induced by P. gingivalis lipid A but not compound 506 in alveolar macrophages. A CaM kinase activator reduced the induction of IL-1β in the serum of mice when administered with compound 506, and protected the mice against the lethal toxicity. The modulation of a variety of intracellular enzymes including the CaM kinase may result in clinical control of endotoxic sepsis.