Endothelin-1 production by the canine macrophage cell line DH82: Enhanced production in response to microbial challenge

Divino, Jeffrey N.; Chawla, Kashmira S.; Silva, Christina M. da; Bjorge, Ashley M.; Brittingham, Andrew

doi:10.1016/j.vetimm.2010.02.006

Cited by 5 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Brain endothelial cells, microglia, astrocytes, and neurons are other sources of ET-1 (78,84). We observed endogenous secretion levels comparable to those found in DH82 cells by Divino et al (37), but we did not observe the reported stimulation with LPS. Methodological differences from that study included DH82 passage levels (85), the preparation of LPS (E. coli O111:B4 versus O127:B8), and endpoint after stimulation (48 h versus 24 h or less).…”

Section: Discussionsupporting

confidence: 77%

See 1 more Smart Citation

Cellular Microbiology of Mycoplasma canis

et al. 2016

View full text Add to dashboard Cite

M ycoplasma canis infects many mammalian hosts but is usually thought of as a commensal or opportunistic cofactor in respiratory or urogenital tract diseases of dogs (1). We found unexpectedly that M. canis was also detectable by culture or PCR in a majority of brain tissue specimens in a retrospective case-control study of canine granulomatous meningoencephalitis (ME) (GME) and necrotizing ME (NME) (2). The presence of M. canis in brain tissue was associated with both GME and NME (both P Ͻ 0.05, as determined by a 2 test). The clinical signs of this common idiopathic neurological disease of dogs include seizures, proprioceptive deficits, circling, and blindness. Immunosuppressive therapy may be palliative, but the syndrome is progressive and uniformly fatal (3). The extensive search for a presumed viral cause of canine GME and NME has been fruitless (4).In humans, bacterial meningitis and encephalitis are multifactorial lethal infections with often severe sequelae for survivors. New detection methods have shown that the variety of bacteria associated with human ME is much more extensive than usually appreciated (5-9). Additional animal models of bacterial ME are necessary to study this broader spectrum of pathogens (10). Since a possible association between M. canis and canine ME was discovered, our objective has been to help fill the void of basic knowledge about the organism's virulence factors, the host responses that it elicits, and its potential roles in pathogenesis. Our working hypotheses were that M. canis is capable of evoking host cell responses that favor dissemination from mucosal surfaces to secondary sites of infection, possibly in a strain-dependent fashion, and also that, regardless of how it might reach those sites, the presence of M. canis there modulates inflammation and direct injury to host cells. Understanding this potential can be expected to help evaluate the cause of canine ME and other diseases.(Portions of these data were presented in abstract form at Congresses of the International Organization for Mycoplasmology [90,91].) MATERIALS AND METHODSMycoplasma strains and cultivation. Strain PG14 T of M. canis (ATCC 19525) was first isolated from the throat of a normal dog (11). Strains UF31, UF33, LV, 5, 26, Cal, and Mara were first isolated from vaginal swabs of dogs without ME (12). Strains UFG1, UFG2, UFG3, and UFG4 were isolated from frozen brain tissues from cases of canine NME (2). Mycoplasma cynos strain H-831 T (ATCC 27544) was first isolated from the lung of a dog with pneumonia (13). Mycoplasma arginini strain G230 T , Mycoplasma bovigenitalium strain PG11 T , Mycoplasma edwardii strain PG24 T , Mycoplasma maculosum strain Skotti B, Mycoplasma molare strain H542 T , Mycoplasma opalescens strain MH5408 T , and Mycoplasma spumans strain PG13T , representing other species that have been isolated from dogs (1), were obtained from The Mollicutes Collection. All strains were propagated under standard conditions (14) in ATCC 988 medium supplemented with fetal bovine serum (FBS) and glu...

show abstract

Section: Discussionsupporting

confidence: 77%

“…M. canis significantly reduced DH82 cell expression of ET-1 (Fig. 6), in contrast to the increases typically resulting from exposure to other bacteria (37,(79)(80)(81). Once more, the effect was greatest for brain isolate UFG1.…”

Section: Discussionmentioning

confidence: 86%

Cellular Microbiology of Mycoplasma canis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Previous publications support the notion that activation of macrophages induces ET-1 production and release. Specifically, it was recently reported that the canine macrophage cell line, DH82, constitutively secretes both ET-1 and its biologically inactive precursor big ET-1 and that the production of both peptides is increased after either stimulation with LPS from Gram-negative bacteria or with intact and viable Gram-positive and Gramnegative bacteria (42). The secretion of ET-1 by polymorphonuclear neutrophils, macrophages, and mast cells increases during inflammation (43,44).…”

Section: Discussionmentioning

confidence: 99%

A Novel Role of Endothelin-1 in Linking Toll-like Receptor 7-mediated Inflammation to Fibrosis in Congenital Heart Block

Álvarez

Briassouli

Clancy

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Autoimmune associated congenital heart block (CHB) may result from pathogenic cross-talk between inflammatory and profibrosing pathways. Incubation of macrophages with immune complexes (IC) composed of Ro60, a target of the pathologic maternal autoantibodies necessary for CHB, hY3 ssRNA, and affinity-purified anti-Ro60 antibody induces the Toll-like receptor 7 (TLR7)-dependent generation of supernatants that provoke a fibrosing phenotype in human fetal cardiac fibroblasts. We show herein that these cells are a major source of TGF␤ and that endothelin-1 (ET-1) is one of the key components responsible for the profibrosing effects generated by stimulated macrophages. Supernatants from macrophages incubated with IC induced the fibroblast secretion of TGF␤, which was inhibited by treating the macrophages with an antagonist of TLR7. Under the same conditions, the induced fibroblast secretion of TGF␤ was decreased by inhibitors of the ET-1 receptors ETa or ETb or by an anti-ET-1 antibody but not by an isotype control. Exogenous ET-1 induced a profibrosing phenotype, whereas fibroblasts transfected with either ETa or ETb siRNA were unresponsive to the profibrosing effects of the IC-generated macrophage supernatants. Immunohistochemistry of the hearts from two fetuses dying with CHB revealed the presence of ET-1-producing mononuclear cells in the septal region in areas of calcification and fibrosis. In conclusion, these data support a novel role of ET-1 in linking TLR7 inflammatory signaling to subsequent fibrosis and provide new insight in considering therapeutics for CHB.Cardiac conduction defects detected before or at birth, in the absence of structural abnormalities, are strongly associated with maternal autoantibodies to SSA/Ro and/or SSB/La ribonucleoproteins, independent of whether the mother has systemic lupus erythematosus or Sjögren's syndrome or is asymptomatic (1, 2). The mechanism by which maternal anti-SSA/ Ro-SSB/La antibodies initiate and perpetuate inflammation with consequent scarring of the atrioventricular node (the signature lesion of CHB) 2 and endocardium (3) has not been fully defined. One proposed pathologic cascade centers apoptosis of the fetal cardiocytes as the cellular event that accounts for the surface expression of the otherwise intracellular target antigens (4 -6), facilitating subsequent opsonization by circulating maternal autoantibodies. Experimental data suggest that hY3 ssRNA associated with the SSA/Ro protein bound by affinitypurified anti-Ro60 antibody (AP60) gains access to the macrophage endosome via Fc␥R uptake with subsequent ligation of the Toll-like receptor 7 (TLR7). In clearing the opsonized apoptotic cardiomyocytes, infiltrating macrophages secrete factors that promote a scarring phenotype of the resident cardiac fibroblasts, as evidenced by their transdifferentiation to myofibroblasts and production of collagen (7,8).Immunohistochemical studies (5) of hearts from several fetuses dying with CHB demonstrate abundant TGF␤ in the septal region. TGF␤ probably contributes to s...

show abstract

“…ET-1 is a peptide consisting of 21 amino acids and is mainly secreted by endothelial cells [ 28 ]. It has a strong vasoconstrictive effect and plays an important role in maintaining the basal vascular tone and cardiovascular homeostasis [ 29 , 30 ]. Researchers have found a close relationship between ET-1 and intestinal inflammation, which is a chronic inflammatory bowel disease that includes ulcerative colitis and Crohn’s disease [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Aspirin Caused Intestinal Damage through FXR and ET-1 Signaling Pathways

Lin,

Zhang,

Dai

et al. 2024

IJMS

View full text Add to dashboard Cite

Aspirin is a non-steroidal, anti-inflammatory drug often used long term. However, long-term or large doses will cause gastrointestinal adverse reactions. To explore the mechanism of intestinal damage, we used non-targeted metabolomics; farnesoid X receptor (FXR) knockout mice, which were compared with wild-type mice; FXR agonists obeticholic acid (OCA) and chenodeoxycholic acid (CDCA); and endothelin-producing inhibitor estradiol to explore the mechanisms of acute and chronic intestinal injuries induced by aspirin from the perspective of molecular biology. Changes were found in the bile acids taurocholate acid (TCA) and tauro-β-muricholic acid (T-β-MCA) in the duodenum, and we detected a significant inhibition of FXR target genes. After additional administration of the FXR agonists OCA and CDCA, duodenal villus damage and inflammation were effectively improved. The results in the FXR knockout mice and wild-type mice showed that the overexpression of endothelin 1 (ET-1) was independent of FXR regulation after aspirin exposure, whereas CDCA was able to restore the activation of ET-1, which was induced by aspirin in wild-type mice in an FXR-dependent manner. The inhibition of ET-1 production could also effectively protect against small bowel damage. Therefore, the study revealed the key roles of the FXR and ET-1 pathways in acute and chronic aspirin-induced intestinal injuries, as well as strategies on alleviating aspirin-induced gastrointestinal injury by activating FXR and inhibiting ET-1 overexpression.

show abstract

Endothelin-1 production by the canine macrophage cell line DH82: Enhanced production in response to microbial challenge

Cited by 5 publications

References 50 publications

Cellular Microbiology of Mycoplasma canis

Cellular Microbiology of Mycoplasma canis

A Novel Role of Endothelin-1 in Linking Toll-like Receptor 7-mediated Inflammation to Fibrosis in Congenital Heart Block

Aspirin Caused Intestinal Damage through FXR and ET-1 Signaling Pathways

Contact Info

Product

Resources

About