Association between chronic liver and colon inflammation during the development of murine syngeneic graft-versus-host disease

Brandon, J. Anthony; Perez, Jacqueline; Jennings, C. Darrell; Cohen, Donald A.; Sindhava, Vishal; Bondada, Subbarao; Kaplan, Alan M.; Bryson, J. Scott

doi:10.1152/ajpgi.00511.2009

Cited by 8 publications

(16 citation statements)

References 62 publications

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“…A goat-nonspecific IgG was from R&D Systems (Minneapolis, MN). A rabbit polyclonal anti-TLR5 Ab (IMG-580) specific to 300 -350-amino-acid residue, which is a part of extracellular and flagellin-binding domains (7,15), was purchased from IMGENEX and used for both the immunofluorescence and Western blotting. All other chemicals used were purchased from Sigma.…”

Section: Methodsmentioning

confidence: 99%

Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands

Muramatsu

Tamada²,

Nara

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Airway serous secretion is essential for the maintenance of mucociliary transport in airway mucosa, which is responsible for the upregulation of mucosal immunity. Although there are many articles concerning the importance of Tolllike receptors (TLRs) in airway immune systems, the direct relationship between TLRs and airway serous secretion has not been well investigated. Here, we focused on whether TLR5 ligand flagellin, which is one of the components of Pseudomonas aeruginosa, is involved in the upregulation of airway serous secretion. Freshly isolated swine tracheal submucosal gland cells were prepared, and the standard patch-clamp technique was applied for measurements of the whole cell ionic responses of these cells. Flagellin showed potentiating effects on these oscillatory currents induced by physiologically relevant low doses of acetylcholine (ACh) in a dose-dependent manner. These potentiating effects were TLR5 dependent but TLR4 independent. Both nitric oxide (NO) synthase inhibitors and cGMPdependent protein kinase (cGK) inhibitors abolished these flagellininduced potentiating effects. Furthermore, TLR5 was abundantly expressed on tracheal submucosal glands. Flagellin/TLR5 signaling further accelerated the intracellular NO synthesis induced by ACh. These findings suggest that TLR5 takes part in the airway mucosal defense systems as a unique endogenous potentiator of airway serous secretions and that NO/cGMP/cGK signaling is involved in this rapid potentiation by TLR5 signaling. Ca 2ϩ -activated Cl Ϫ channel; nitric oxide; cGMP-dependent protein kinase; patch-clamp; Pseudomonas aeruginosa TRACHEAL SUBMUCOSAL GLANDS secrete mucin, various enzyme proteins, and electrolytes (therefore, water), which serve as a nonspecific airway defense mechanism. Additionally, submucosal glands secrete immunoglobulins to neutralize many microbes, serving as a specific airway defense mechanism (34). Among these airway mucosal defense systems, airway serous secretion plays important roles in hydrating airway surfaces and flushing mucin glycoproteins out of the ducts, contributing to the maintenance of mucociliary transport (2,4,10,24,48). Human, feline, and swine tracheal gland acinar cells generate ionic currents in response to relatively low doses of cholinergic and ␣-adrenergic stimuli, and these currents are activated by the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) raised by these neurotransmitters (16,31,38,44,45). The Ca 2ϩ -activated Cl Ϫ channel (CaCC) may play an important role in physiological basal secretions in the airways. It has recently become known that CaCC composes a newly identified transmembrane protein with unknown function, 16, Ano 1 (TMEM16A), which exists in both the airway surface epithelium and submucosal glands (28,33). Concerning the electrophysiological characteristics of CaCC, we have reported that tyrosine kinase, cyclic-ADP ribose, and nitric oxide (NO)/cGMP/cGMP-dependent protein kinase (cGK) are involved in the intracellular pathway of oscillatory ionic currents evoked by low doses ...

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Section: Methodsmentioning

confidence: 99%

Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands

Muramatsu

Tamada²,

Nara

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…CD4(+) T cells were found in the peribiliary region of the liver of animals with syngeneic GVHD. This model is useful to study the entero-hepatic linkage between the two sites of inflammation [21].…”

Section: Contribution Of Experimental Models Of Gvhd To Understandingmentioning

confidence: 99%

Liver Graft versus Host Disease after Allogeneic Peripheral Stem Cell Transplantation: Update on Etiopathogenesis and Diagnosis

Mihăilă

2016

Romanian Journal of Internal Medicine

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Graft versus host disease (GVHD) is the main complication of allogeneic hematopoietic cell transplantation and is more frequent after peripheral stem cell transplants. Graft versus leukemia or lymphoma component of them is beneficial to eradicate residual tumor mass after previous treatment and conditioning regimen. A severe GVHD may endanger the patient's life. The most important liver manifestations of GVHD are increased serum alkaline phosphatase and bilirubin values. The last allows to estimate the GVHD severity. Sometimes, an increase of aminotransferases can mimic an acute hepatitis. Donor-derived hematopoietic cells appeared to turn in mesenchymal liver cells. Activated CD4(+) T cells, humoral and complement activation, a large number of cytokines and cytokine receptors are involved in GVHD development. Correct and early recognition of GVHD and its differentiation from the other liver diseases are essential for the medical practice.

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“…These findings are interesting and support our recent publication that suggests that the colon and liver inflammation that occurs in this inducible disease are linked via T-cell responsiveness to the microbiota. 14 Finally, since murine SGVHD was characterized by an increased CD4 + T-cell immune response against microbial Ag, it was important to link the reduction in the putative microbial antigen source with decreased in vitro CD4 + T-cell proliferation to microbial antigen. Broad spectrum antibiotic therapy inhibited significantly the enhanced T-cell proliferative response against the CeAg preparation, but in addition, there was also a reduction in T H 17 and T H 1 cytokines that have been associated with development of SGVHD.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…It should be noted that LPS appeared not to be required for disease induction as disease was induced in both LPS responsive and hypo-responsive animals. 22 As TLR expression is increased in SGVHD animals, 14 stimulation through other TLR ligands may participate in the development of SGVHD and a reduction in the microbiota may reduce proinflammatory responses. It is also clear that following lethal irradiation and CsA therapy the treated animals are lymphopenic and it is likely that reconstitution of CD4 + T cells may occur via specific and nonspecific proliferative responses.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…[10][11][12][13] Given the similarities between colitis models and murine SGVHD we initially determined that there was an increased CD4 + T-cell-mediated in vitro anti-microbial Ag response in T cells isolated from SGVHD animals relative to transplant control animals. 6,14 These studies were expanded to show that the T-cell response was specific for microbial antigens, was MHC class II restricted and virtually all of the proliferative activity was observed in the activated/memory subset of CD4 + T cells. 15 Importantly, no response was observed against syngeneic DC or DC pulsed with protein lysates isolated from syngeneic colonic epithelial lines, demonstrating a lack of in vitro autoreactivity.…”

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confidence: 99%

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A gut feeling about murine syngeneic GVHD

et al. 2011

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Association between chronic liver and colon inflammation during the development of murine syngeneic graft-versus-host disease

Abstract: AM, Bryson JS. Association between chronic liver and colon inflammation during the development of murine syngeneic graft-versus-host disease.

Cited by 8 publications

References 62 publications

Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands

Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands

Liver Graft versus Host Disease after Allogeneic Peripheral Stem Cell Transplantation: Update on Etiopathogenesis and Diagnosis

A gut feeling about murine syngeneic GVHD

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