A human monoclonal anti-TNF alpha antibody (adalimumab) reduces airway inflammation and ameliorates lung histology in a murine model of acute asthma

Çatal, Ferhat; Mete, Emin; Tayman, Cüneyt; Topal, Erdem; Albayrak, Abdulmecit; Sert, Hüseyin

doi:10.1016/j.aller.2013.11.002

Cited by 33 publications

(18 citation statements)

References 22 publications

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“…Another study demonstrated that the activation of P2X 7 R in rat immune cells promoted the release of IL-6, IL-1β and TNF-α (33). However, the blockade of TNF-α (using adalimumab) and the silencing of TNF-α has been shown to lead to a prolonged inhibitory effect on inflammation in animal models (34)(35)(36). Our data demonstrated that the increasing trend in the expression of IL-1β, IL-6, and TNF-α in the knee joint cartilage tissue of rats with OA was reversed by the P2X 7 R antagonist, AZD9056.…”

Section: Discussionmentioning

confidence: 99%

Blocking of the P2X7 receptor inhibits the activation of the MMP-13 and NF-κB pathways in the cartilage tissue of rats with osteoarthritis

Yang

et al. 2016

International Journal of Molecular Medicine

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P2X purinoceptor 7 (P2X7) receptor (P2X7R) is known to play a significant role in inflammation and pain-causing diseases, including osteoarthritis (OA). However, the mechanisms of action of P2X7R and its role in OA remain unclear. The articular cartilage is the crucial region in which pathological changes occur in OA, involving the dysregulation of degradation and maintenance mechanisms. In this study, we aimed to reveal the molecular mechanisms of action of P2X7R in articular cartilage in OA-induced pain and inflammation by using AZD9056, an antagonist of P2X7R. We created an animal model of OA by using Wistar rats administered (by intra-articular injection) monosodium iodoacetate (MIA), and the rats with OA were then treated with the P2X7R antagonist, AZD9056. We found that treatment with AZD9056 exerted pain-relieving and anti-inflammatory effects. Importantly, we found that the upregulated expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase-13 (MMP-13), substance P (SP) and prostaglandin E2 (PGE2) which was induced by MIA in cartilage tissues was reversed by AZD9056. Western blot analysis was used to examine the expression of inhibitor of nuclear factor-κB (NF-κB) kinase (IKK)α, IKKβ, inhibitor of NF-κB (IκB)α, NF-κB p65 and their phosphorylation forms; they were found to be significantly increased in the knee cartilage tissues from rats with OA; however, opposite effects were observed by the injection of AZD9056. These results implied that P2X7R was associated with the activation of the NF-κB pathway in the development of OA. Our results also revealed that helenalin, an NF-κB pathway inhibitor, decreased the expression of P2X7R, IL-1β, IL-6, TNF-α, SP, PGE2 and MMP-13, which was induced by MIA, in the knee cartilage tissues of rats with OA. On the whole, our findings suggest that P2X7R regulates the MMP-13 and NF-κB pathways in cartilage tissue and mediate OA-induced pain and inflammation.

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Section: Discussionmentioning

confidence: 99%

Blocking of the P2X7 receptor inhibits the activation of the MMP-13 and NF-κB pathways in the cartilage tissue of rats with osteoarthritis

Yang

et al. 2016

International Journal of Molecular Medicine

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“…Methacholine-induced airway hyperreactivity was also inhibited by infliximab. Similarly, in a murine model of acute asthma, adalimumab therapy reduced lung inflammation and inflammatory cell infiltration (Catal et al, 2014). Local administration of TNFα antisense nucleotide has also been reported to suppress allergic inflammation in mice by reducing release of TNFα and other Th2 cytokines, mucus secretion and inflammatory cell influx (Luo et al, 2012).…”

Section: Role Of Tnfα In Pulmonary Diseasesmentioning

confidence: 99%

Anti-TNFα therapy in inflammatory lung diseases

Malaviya

Laskin

2017

Pharmacology & Therapeutics

186

137

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Increased levels of tumor necrosis factor (TNF) α have been linked to a number of pulmonary inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sarcoidosis, and interstitial pulmonary fibrosis (IPF). TNFα plays multiple roles in disease pathology by inducing an accumulation of inflammatory cells, stimulating the generation of inflammatory mediators, and causing oxidative and nitrosative stress, airway hyperresponsiveness and tissue remodeling. TNF-targeting biologics, therefore, present a potentially highly efficacious treatment option. This review summarizes current knowledge on the role of TNFα in pulmonary disease pathologies, with a focus on the therapeutic potential of TNFα-targeting agents in treating inflammatory lung diseases.

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“…Moreover, in the past decade, several strategies have been proposed to target TNF receptor as a treatment for asthma (i.e. adalimumab, etanercep, infliximab) 56, 57 and rheumatoid arthritis (i.e. in the DREAM Challenge 8.5 58 , in several cohorts with similar surveys 59–61 and in ref.…”

Section: Discussionmentioning

confidence: 99%

Genetic and functional characterization of disease associations explains comorbidity

Rubio-Pérez

Güney

Aguilar

et al. 2017

Sci Rep

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Understanding relationships between diseases, such as comorbidities, has important socio-economic implications, ranging from clinical study design to health care planning. Most studies characterize disease comorbidity using shared genetic origins, ignoring pathway-based commonalities between diseases. In this study, we define the disease pathways using an interactome-based extension of known disease-genes and introduce several measures of functional overlap. The analysis reveals 206 significant links among 94 diseases, giving rise to a highly clustered disease association network. We observe that around 95% of the links in the disease network, though not identified by genetic overlap, are discovered by functional overlap. This disease network portraits rheumatoid arthritis, asthma, atherosclerosis, pulmonary diseases and Crohn’s disease as hubs and thus pointing to common inflammatory processes underlying disease pathophysiology. We identify several described associations such as the inverse comorbidity relationship between Alzheimer’s disease and neoplasms. Furthermore, we investigate the disruptions in protein interactions by mapping mutations onto the domains involved in the interaction, suggesting hypotheses on the causal link between diseases. Finally, we provide several proof-of-principle examples in which we model the effect of the mutation and the change of the association strength, which could explain the observed comorbidity between diseases caused by the same genetic alterations.

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A human monoclonal anti-TNF alpha antibody (adalimumab) reduces airway inflammation and ameliorates lung histology in a murine model of acute asthma

Abstract: Adalimumab (a human monoclonal anti-TNF alpha antibody) therapy significantly reduced the severity of lung damage by decreasing cellular infiltration and improvement on the lung histology in a murine model of acute asthma.

Cited by 33 publications

References 22 publications

Blocking of the P2X7 receptor inhibits the activation of the MMP-13 and NF-κB pathways in the cartilage tissue of rats with osteoarthritis

Blocking of the P2X7 receptor inhibits the activation of the MMP-13 and NF-κB pathways in the cartilage tissue of rats with osteoarthritis

Anti-TNFα therapy in inflammatory lung diseases

Genetic and functional characterization of disease associations explains comorbidity

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