Effects of IL‐1β, TNF‐α, and macrophage migration inhibitory factor on prostacyclin synthesis in rat pulmonary artery smooth muscle cells

Itoh, Akichika; Nishihira, Jun; Makita, Hironi; Miyamoto, Kenji; Yamaguchi, Etsuro; Nishimura, Masaharu

doi:10.1046/j.1440-1843.2003.00491.x

Cited by 47 publications

(42 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MIF, a critical upstream regulator of inflammation, inhibits prostacyclin synthase expression in animal models of hypoxiainduced pulmonary hypertension and is associated with pulmonary artery smooth-muscle cell proliferation. 24,25 Studies involving other diseases have also shown that MIF can activate aromatase and increase estradiol levels. 26 Additionally, MIF has been implicated in the pathogenesis of several autoimmune diseases, including autoimmune liver disease, [27][28][29][30] which is a known risk factor for POPH.…”

Section: Discussionmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor as a Novel Biomarker of Portopulmonary Hypertension

et al. 2016

View full text Add to dashboard Cite

Portopulmonary hypertension (POPH) is a poorly understood complication of liver disease associated with significant morbidity and mortality. We sought to identify novel biomarkers of POPH disease presence and severity. We performed a prospective, multicenter, case-control study involving patients with liver disease undergoing right heart catheterization. POPH cases were defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg and pulmonary vascular resistance (PVR) >240 dynes˙s˙cm. Plasma samples were collected from the systemic and pulmonary circulation, and antibody microarray was used to identify biomarkers. Characterization and validation of a candidate cytokine, macrophage migration inhibitory factor (MIF), was performed using enzyme-linked immunosorbent assay. Continuous variables were compared using a Mann-Whitney U test and correlated with disease severity using Spearman correlation. MIF levels were elevated in both the systemic and pulmonary circulation in patients with POPH compared with controls .53], P = 0.002). In patients with POPH, MIF levels were positively correlated with PVR (r = 0.58, P = 0.006) and inversely correlated with cardiac output (r = −0.57, P = 0.007). MIF >60 ng/mL or tricuspid regurgitation gradient >50 mmHg had a 92% sensitivity and specificity for the diagnosis of POPH, with a positive predictive value of 86% and a negative predictive value of 96%. MIF is a promising novel biomarker of POPH disease presence and severity in patients with liver disease and portal hypertension.

show abstract

Section: Discussionmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor as a Novel Biomarker of Portopulmonary Hypertension

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Although not specifically tested in these studies, it is likely that PGI 2 exerts its effects primarily by acutely decreasing the secretion of ghrelin from these enteric cells. IL-1b has been previously shown to increase the production of PGI 2 in numerous other tissues, primarily by upregulating the expression and action of COX-2 (Belt et al 1999, Caughey et al 2001, Walch and Morris 2002, Itoh et al 2003. Obviously, one of the outcomes of this acute decrease in circulating ghrelin would be the development of anorexia as is typical of the acute illness response.…”

Section: Discussionmentioning

confidence: 99%

Prostacyclin signaling regulates circulating ghrelin during acute inflammation

Madison

Scarlett

Levasseur

et al. 2007

Journal of Endocrinology

View full text Add to dashboard Cite

Ghrelin is an octanoylated 28 amino acid peptide predominantly secreted by the stomach, and has potent stimulatory effects on appetite. Several laboratories, including our own, have demonstrated that ghrelin levels fall in states of acute inflammation brought about by injection of bacterial lipopolysaccharide (LPS). We now demonstrate that the decrease in circulating ghrelin is not due to a decrease in ghrelin gene expression, but is instead likely to be due to an acute decrease in ghrelin secretion. Furthermore, we have found that the change in circulating ghrelin during acute inflammation required a prostaglandin second messenger, but did not require the synthesis of nitric oxide. Interestingly, i.v. injection of prostaglandin E 2 failed to decrease circulating ghrelin levels, whereas prostacyclin decreased circulating ghrelin to a similar extent as did LPS. We also provide anatomical evidence for the mechanism of the regulation of ghrelin by inflammation. We demonstrate that the type 1 interleukin-1b (IL-1b) receptor is expressed within the gastric mucosa, but is not expressed by ghrelin cells. The prostacyclin receptor was also expressed in the gastric mucosa, and the majority of ghrelin-producing cells were found to co-express this receptor. Mice with genetic deletion of the type 1 IL-1 receptor do not suppress circulating ghrelin levels with LPS administration. Collectively, these data support a model in which the mechanism of inflammation induced decreases in ghrelin are due to the action of IL-1b on cells within the gastric mucosa that in turn produce prostacyclin as a second messenger. These data provide further support for the potential role of ghrelin as a therapeutic agent in acute and chronic inflammatory diseases.

show abstract

“…[105][106][107]111,112,114,124 Several reports indicate that the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-␣) plays a role in nondiabetic painful neuropathy. [125][126][127] It is quite plausible that it also plays a role in diabetic neuropathic pain (as has been suggested 128,129 ), because TNF-␣ expression is increased in tissues of diabetic animals, and TNF-␣ induces overexpression of cyclooxygenase-2, 130,131 also implicated in diabetic hyperalgesia and allodynia. 97,99 TNF-␣ antagonists have never been tested in models of diabetic painful neuropathy.…”

Section: Strategies For Drug Discoverymentioning

confidence: 95%

Diabetic Painful and Insensate Neuropathy: Pathogenesis and Potential Treatments

2009

View full text Add to dashboard Cite

Summary:Advanced peripheral diabetic neuropathy (PDN) is associated with elevated vibration and thermal perception thresholds that progress to sensory loss and degeneration of all fiber types in peripheral nerve. A considerable proportion of diabetic patients also describe abnormal sensations such as paresthesias, allodynia, hyperalgesia, and spontaneous pain. One or several manifestations of abnormal sensation and pain are described in all the diabetic rat and mouse models studied so far (i.e., streptozotocin-diabetic rats and mice, type 1 insulinopenic BB/Wor and type 2 hyperinsulinemic diabetic BBZDR/Wor rats, Zucker diabetic fatty rats, and nonobese diabetic, Akita, leptin-and leptin-receptor-deficient, and highfat diet-fed mice). Such manifestations are 1) thermal hyperalgesia, an equivalent of a clinical phenomenon described in early PDN; 2) thermal hypoalgesia, typically present in advanced PDN; 3) mechanical hyperalgesia, an equivalent of pain on pressure in early PDN; 4) mechanical hypoalgesia, an equivalent to the loss of sensitivity to mechanical noxious stimuli in advanced PDN; 5) tactile allodynia, a painful perception of a light touch; and 5) formalin-induced hyperalgesia. Rats with short-term diabetes develop painful neuropathy, whereas those with longer-term diabetes and diabetic mice typically display manifestations of both painful and insensate neuropathy, or insensate neuropathy only. Animal studies using pharmacological and genetic approaches revealed important roles of increased aldose reductase, protein kinase C, and poly(ADPribose) polymerase activities, advanced glycation end-products and their receptors, oxidative-nitrosative stress, growth factor imbalances, and C-peptide deficiency in both painful and insensate neuropathy. This review describes recent achievements in studying the pathogenesis of diabetic neuropathic pain and sensory disorders in diabetic animal models and developing potential pathogenetic treatments. Key Words: Animal models, diabetic insensate neuropathy, diabetic painful neuropathy, formalin-induced hyperalgesia, mechanical hyper-and hypoalgesia, pathogenetic treatments of diabetic neuropathic pain and sensory loss, symptomatic treatments of diabetic pain, tactile allodynia, thermal hyper-and hypoalgesia.

show abstract

Effects of IL‐1β, TNF‐α, and macrophage migration inhibitory factor on prostacyclin synthesis in rat pulmonary artery smooth muscle cells

Abstract: These results suggest that TNF-alpha and MIF are potentially antagonistic to the action of PGI2 in rat PASMCs via down-regulation of PGIS mRNA. Simultaneous induction of COX-2 mRNA may further counteract the action of PGI2 by increasing the levels of eicosanoids other than PGI2.

Cited by 47 publications

References 28 publications

Macrophage Migration Inhibitory Factor as a Novel Biomarker of Portopulmonary Hypertension

Macrophage Migration Inhibitory Factor as a Novel Biomarker of Portopulmonary Hypertension

Prostacyclin signaling regulates circulating ghrelin during acute inflammation

Diabetic Painful and Insensate Neuropathy: Pathogenesis and Potential Treatments

Contact Info

Product

Resources

About