Antifibrosis: To Reverse the Irreversible

Paz, Ziv; Shoenfeld, Yehuda

doi:10.1007/s12016-009-8157-7

Cited by 35 publications

(23 citation statements)

References 132 publications

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“…Drugs controlling the formation and activity of TGF-, such as anti-TGF- monoclonal antibodies and pirfenidone, a drug which inhibit fibroblast activation, hold great promise and were subject to clinical development [51]; however, their therapeutic efficacy on patients with lung fibrosis, especially IPF, still remains to be clearly defined [52]. On the other hand, the strategy of targeting prostaglandin synthesis by COX inhibitors is still controversial.…”

Section: Discussionmentioning

confidence: 99%

Role of histamine H 4 receptor ligands in bleomycin-induced pulmonary fibrosis

Lucarini

Pini

Rosa

et al. 2016

Pharmacological Research

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Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The results here reported clearly demonstrated that H 4 R ligands have a beneficial effect in a model of lung fibrosis in the mouse, thus indicating that H 4 R antagonists or inverse agonists could be a novel therapeutic strategy for lung inflammatory diseases.4

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Section: Discussionmentioning

confidence: 99%

Role of histamine H 4 receptor ligands in bleomycin-induced pulmonary fibrosis

Lucarini

Pini

Rosa

et al. 2016

Pharmacological Research

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“…Chronic inflammatory conditions in the lungs lead to permanent structural changes and remodeling of the airway walls, whose fibrosis is a major constituent. Nowadays, there are no approved drugs that counteract the pathologic mechanism apart from some potential treatments targeting the TGF-b1 pathway, e.g., pirfenidone (Paz and Shoenfeld, 2010). Our experiments were performed in C57BL/6 mice, which are reported to be more susceptible to bleomycin-induced fibrosis than other strains, such as BALB/c mice (Schrier et al, 1983;Harrison and Lazo, 1987).…”

Section: Discussionmentioning

confidence: 99%

Prevention of Bleomycin-Induced Lung Inflammation and Fibrosis in Mice by Naproxen and JNJ7777120 Treatment

Rosa

Pini

Lucarini

et al. 2014

J Pharmacol Exp Ther

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Pulmonary fibrosis, a progressive and lethal lung disease characterized by inflammation and accumulation of extracellular matrix components, is a major therapeutic challenge for which new therapeutic strategies are warranted. Cyclooxygenase (COX) inhibitors have been previously utilized to reduce inflammation. Histamine H 4 receptor (H 4 R), largely expressed in hematopoietic cells, has been identified as a novel target for inflammatory and immune disorders. The aim of this study was to evaluate the effect of JNJ7777120 (1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine), a selective H 4 R antagonist, and naproxen, a well known nonsteroidal anti-inflammatory drug, and their combination in a murine model of bleomycin-induced fibrosis. Bleomycin (0.05 IU) was instilled intratracheally to C57BL/6 mice, which were then treated by micro-osmotic pump with vehicle, JNJ7777120 (40 mg/kg b.wt.), naproxen (21 mg/kg b.wt.), or a combination of both. Airway resistance to inflation, an index of lung stiffness, was assessed, and lung specimens were processed for inflammation, oxidative stress, and fibrosis markers. Both drugs alone were able to reduce the airway resistance to inflation induced by bleomycin and the inflammatory response by decreasing COX-2 and myeloperoxidase expression and activity and thiobarbituric acid-reactive substance and 8-hydroxy-29-deoxyguanosine production. Lung fibrosis was inhibited, as demonstrated by the reduction of tissue levels of transforming growth factor-b, collagen deposition, relative goblet cell number, and smooth muscle layer thickness. Our results demonstrate that both JNJ7777120 and naproxen exert an anti-inflammatory and antifibrotic effect that is increased by their combination, which could be an effective therapeutic strategy in the treatment of pulmonary fibrosis.

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“…The process occurs normally in the formation of scar tissue to replace normal tissue lost through injury, infection or chronic liver insults (1)(2)(3)(4)(5). The cells responsible for extracellular matrix (ECM) fiber formation are hepatic stellate cells (HSCs), which enhance cell proliferation at the onset of liver injury (6).…”

Section: Introductionmentioning

confidence: 99%