Etanercept Exacerbates Inflammation and Pathology in a Rabbit Model of Active Pulmonary Tuberculosis

Tsenova, Liana; O'Brien, Paul Edmond; Holloway, Jennifer; Peixoto, Blas; Soteropoulos, Patricia; Fallows, Dorothy; Kaplan, Gilla; Subbian, Selvakumar

doi:10.1089/jir.2013.0123

Cited by 20 publications

(17 citation statements)

References 53 publications

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“…Moreover, it will be important to characterize the expressed repertoire of TRA and TRD chains in multiple tissues and immune contexts, in which specific T cell subsets might be amplified upon particular selection pressures. The rabbit remains an excellent experimental model for several infectious diseases for which rodents are not fully relevant, including tuberculosis, syphilis and papillomaviruses . Our data will be useful for future studies of immune responses in this species.…”

Section: Resultsmentioning

confidence: 99%

The T cell receptor (TRA) locus in the rabbit (Oryctolagus cuniculus): Genomic features and consequences for invariant T cells

et al. 2019

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The rabbit has been widely used in immunology and infectiology. Rabbit immunoglobulins have been extensively studied, leading to the discovery of their idiotypes, allotypic diversity, and of the diversification of the primary repertoire by hyperconversion. Much less is known about rabbit T cell receptors (TR), especially TRA. This isotype is particularly important for innate-like T cells, which typically express invariant TRA (iTRA). The presence of such cells in the rabbit remains an enigma. Rabbit NKT cells seem to be very rare, and lagomorphs lack MAIT cells. TRAV1, the variable gene expressed in the iTRA of these cells across most mammals, and MR1, the MH1-like receptor that present riboflavin derivatives to MAIT cells, are missing in rabbit. An alternative iTRA has been identified, that may be expressed by new innate-like T cells. To facilitate TRA repertoire analyses in rabbit, we report here a full description of TRA and TRD loci and a subgroup definition based on IMGT R classification. Rabbit TRA rearrangements follow the same temporal pattern that is observed in mouse and human. Rare transcripts expressing TRDV/TRDD/TRDJ rearrangements spliced to TRAC were detected. TRA and TRD genes have been made available in IMGT and IMGT/HighV-QUEST, allowing easy analysis of TRA/TRD RepSeq.

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Section: Resultsmentioning

confidence: 99%

The T cell receptor (TRA) locus in the rabbit (Oryctolagus cuniculus): Genomic features and consequences for invariant T cells

et al. 2019

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“…For example, the genes of the brown module are significantly associated with the biological pathways of Tuberculosis, Staphylococcus aureus infection, Leishmaniasis, Pertussis, and Legionellosis. All these pathways play critical roles in infections and remodeling in COPD (Carette et al 2018;Tsenova et al 2014;Ziesemer et al 2018;Sabulski et al 2017). In the brown module, eight hub DEGs including CYp27A1, GM2A, LGAL59, SPI1, PARVG, LOC644189, NLRC4, CD300LF are considered as the novel genes in the COPD.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers in common chronic lung diseases by co-expression networks and drug-target interactions analysis

Maghsoudloo

Jamalkandi²,

Najafi³

et al. 2020

Mol Med

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Background: asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are three serious pulmonary diseases that contain common and unique characteristics. Therefore, the identification of biomarkers that differentiate these diseases is of importance for preventing misdiagnosis. In this regard, the present study aimed to identify the disorders at the early stages, based on lung transcriptomics data and drug-target interactions. Methods: To this end, the differentially expressed genes were found in each disease. Then, WGCNA was utilized to find specific and consensus gene modules among the three diseases. Finally, the disease-disease similarity was analyzed, followed by determining candidate drug-target interactions. Results: The results confirmed that the asthma lung transcriptome was more similar to COPD than IPF. In addition, the biomarkers were found in each disease and thus were proposed for further clinical validations. These genes included RBM42, STX5, and TRIM41 in asthma, CYP27A1, GM2A, LGALS9, SPI1, and NLRC4 in COPD, ATF3, PPP1R15A, ZFP36, SOCS3, NAMPT, and GADD45B in IPF, LRRC48 and CETN2 in asthma-COPD, COL15A1, GIMAP6, and JAM2 in asthma-IPF and LMO7, TSPAN13, LAMA3, and ANXA3 in COPD-IPF. Finally, analyzing drug-target networks suggested anti-inflammatory candidate drugs for treating the above mentioned diseases. Conclusion: In general, the results revealed the unique and common biomarkers among three chronic lung diseases. Eventually, some drugs were suggested for treatment purposes.

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“…Both mice and rabbits treated with CC-11050 or CC-3052 alone retained their ability to control Mtb growth as the infection progressed, indicating that adaptive immunity was not adversely affected. In contrast, uncontrolled bacillary replication in the lungs was a characteristic of generalized immune suppression, induced in mice by treatment with anti-TNF antibody or in rabbits treated with the soluble TNF receptor etanercept ( 11 , 28 ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic Inhibition of Host Phosphodiesterase-4 Improves Isoniazid-Mediated Clearance of Mycobacterium tuberculosis

et al. 2016

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The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics and explored the mechanism underlying the efficacy of a more potent PDE4i, CC-11050, as adjunct to INH treatment in a mouse model of pulmonary Mtb infection. Genome-wide lung transcriptome analysis confirmed the dampening of inflammation and associated network genes that we previously reported with CC-3052. Consistent with the reduction in inflammation, a significant improvement in Mtb control and pathology was observed in the lungs of mice treated with CC-11050 plus INH, compared to INH alone. This important confirmatory study will be used to help design upcoming human clinical trials with CC-11050 as an HDT for TB treatment.

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Etanercept Exacerbates Inflammation and Pathology in a Rabbit Model of Active Pulmonary Tuberculosis

Cited by 20 publications

References 53 publications

The T cell receptor (TRA) locus in the rabbit (Oryctolagus cuniculus): Genomic features and consequences for invariant T cells

The T cell receptor (TRA) locus in the rabbit (Oryctolagus cuniculus): Genomic features and consequences for invariant T cells

Identification of biomarkers in common chronic lung diseases by co-expression networks and drug-target interactions analysis

Pharmacologic Inhibition of Host Phosphodiesterase-4 Improves Isoniazid-Mediated Clearance of Mycobacterium tuberculosis

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