Immediate Release of Gastrin-Releasing Peptide Mediates Delayed Radiation-Induced Pulmonary Fibrosis

Tighe, Robert; Heck, Karissa; Soderblom, Erik J.; Zhou, Shutang; Birukova, Anastasiya; Young, Kenneth H.; Rouse, Doris J.; Vidas, Jessica; Komforti, Miglena K.; Toomey, Christopher B.; Cuttitta, Frank; Sunday, Mary E.

doi:10.1016/j.ajpath.2019.01.017

Cited by 9 publications

(14 citation statements)

References 45 publications

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“…Moreover, antagonizing GRP receptors decreased IL‐8‐driven neutrophil chemotaxis in vitro independently of CXCR2 internalization and induced activation of MAPKs (p38 and ERK1/2) and down‐regulation of neutrophil adhesion molecules CD11b and CD66b (Czepielewski et al, 2017). GRP receptors are expressed in the developing lung and increase in response to hypoxia or lung radiation therapy (Tighe et al, 2019). The effect of blocking GRP receptors in the lung, in the context of lung neutrophilia and neutrophil‐induced lung injury remains a question for further studies.…”

Section: Targeting Neutrophils During Rsv Infectionmentioning

confidence: 99%

Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities

Tahamtan

Besteman

Samadizadeh

et al. 2020

British J Pharmacology

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Respiratory syncytial virus (RSV) is an important infectious agent in infants and young children. In most cases, RSV infection only causes mild disease, but in some, it requires invasive ventilation. Although antiviral drugs are obvious candidates to treat viral illness, and some have shown antiviral effects in humans, antivirals such as GS-5806, ALX-0171 and ALS-8176 have not yet met their expectations. Since the inappropriate or dysregulated immune response against RSV leads to harmful immune pathology, a robust immune cascade is probably underway by the time patients reach the hospital. RSV infection is associated with a strong neutrophil influx into the airway. It not clear if these cells contribute to antiviral defence or to lung pathology. This article discusses the protective and harmful roles of neutrophils during RSV infection and provides an overview of mechanisms by which neutrophil function could be targeted to prevent tissue injury and preserve homeostasis.

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Section: Targeting Neutrophils During Rsv Infectionmentioning

confidence: 99%

Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities

Tahamtan

Besteman

Samadizadeh

et al. 2020

British J Pharmacology

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“…Mouse exposure to radiation upregulates urine GRP within the first 24 hours and is associated with radiation-induced pulmonary fibrosis at 15 weeks; blockade of GRP using one dose of an anti-GRP monoclonal antibody administered intraperitoneally at 24 hours postradiation significantly inhibits pulmonary fibrosis at 15 weeks. 41 Murine exposure to influenza stimulates increased GRP in lungs and serum at 4 to 8 days. When influenza-infected mice are treated with anti-GRP antibodies or inhibitors of GRP or GRP receptor at days 2 to 4, the mice have better survival, less inflammation, and diminished cytokine production.…”

Section: Discussionmentioning

confidence: 99%

“…In other mouse models relevant to environmentally induced lung injury, GRP inhibition rescues normal lung structure and increases survival. Mouse exposure to radiation upregulates urine GRP within the first 24 hours and is associated with radiation‐induced pulmonary fibrosis at 15 weeks; blockade of GRP using one dose of an anti‐GRP monoclonal antibody administered intraperitoneally at 24 hours postradiation significantly inhibits pulmonary fibrosis at 15 weeks 41 . Murine exposure to influenza stimulates increased GRP in lungs and serum at 4 to 8 days.…”

Section: Discussionmentioning

confidence: 99%

Urine gastrin‐releasing peptide in the first week correlates with bronchopulmonary dysplasia and post‐prematurity respiratory disease

Voynow

Fisher

Sunday

et al. 2020

Pediatric Pulmonology

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Rationale Bronchopulmonary dysplasia (BPD) is associated with post‐prematurity respiratory disease (PRD) in survivors of extreme preterm birth. Identifying early biomarkers that correlate with later development of BPD and PRD may provide insights for intervention. In a preterm baboon model, elevated gastrin‐releasing peptide (GRP) is associated with BPD, and GRP inhibition mitigates BPD occurrence. Objective We performed a prospective cohort study to investigate whether urine GRP levels obtained in the first postnatal week were associated with BPD, PRD, and other urinary biomarkers of oxidative stress. Methods Extremely low gestational age infants (23‐28 completed weeks) were enrolled in a US multicenter observational study, The Prematurity and Respiratory Outcomes Program (http://clinicaltrials.gov/ct2/show/NCT01435187). We used multivariable logistic regression to examine the association between urine GRP in the first postnatal week and multiple respiratory outcomes: BPD, defined as supplemental oxygen use at 36 + 0 weeks postmenstrual age, and post‐PRD, defined by positive quarterly surveys for increased medical utilization over the first year (PRD score). Results A total of 109 of 257 (42%) infants had BPD, and 120 of 217 (55%) had PRD. On adjusted analysis, GRP level more than 80 was associated with BPD (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.03‐3.25) and positive PRD score (aOR, 2.46; 95% CI, 1.35‐4.48). Urine GRP levels correlated with duration of NICU ventilatory and oxygen support and with biomarkers of oxidative stress: allantoin and 8‐hydroxydeoxyguanosine. Conclusions Urine GRP in the first postnatal week was associated with concurrent urine biomarkers of oxidative stress and with later diagnoses of BPD and PRD.

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“…It can distinguish different stages of pulmonary fibrosis according to the amount of collagen. , To predict RIPF early, we focused on identifying novel biomarkers and developing PET imaging probes. It has been previously reported that blocking the gastrin-releasing peptide receptor (GRPR) in irradiated lung tissue of mice suppresses inflammation by decreasing the number of macrophages and fibroblasts and further reducing the amount of collagen, , indicating that GRPR and GRP mediate the progression of RIPF and are possible targets for the early prediction of RIPF. Previously, our group successfully synthesized the PET imaging probe [ 64 Cu]Cu-NODAGA-galacto-bombesin (BBN) using an analogue of GRP and demonstrated that [ 64 Cu]Cu-NODAGA-galacto-BBN targets GRPR with high affinity .…”

Section: Introductionmentioning

confidence: 99%

Early Prediction of Radiation-Induced Pulmonary Fibrosis Using Gastrin-Releasing Peptide Receptor-Targeted PET Imaging

et al. 2022

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Early diagnosis of radiation-induced pulmonary fibrosis (RIPF) in lung cancer patients after radiation therapy is important. A gastrin-releasing peptide receptor (GRPR) mediates the inflammation and fibrosis after irradiation in mice lungs. Previously, our group synthesized a GRPR-targeted positron emission tomography (PET) imaging probe, [ 64 Cu]Cu-NODA-GA-galacto-bombesin (BBN), an analogue peptide of GRP. In this study, we evaluated the usefulness of [ 64 Cu]Cu-NODAGA-galacto-BBN for the early prediction of RIPF. We prepared RIPF mice and acquired PET/CT images of [ 18 F]F-FDG and [ 64 Cu]Cu-NODAGA-galacto-BBN at 0, 2, 5, and 11 weeks after irradiation (n = 3−10). We confirmed that [ 64 Cu]Cu-NODAGA-galacto-BBN targets GRPR in irradiated RAW 264.7 cells. In addition, we examined whether [ 64 Cu]Cu-NODAGA-galacto-BBN monitors the therapeutic efficacy in RIPF mice (n = 4). As a result, the lung uptake ratio (irradiated-to-normal) of [ 64 Cu]Cu-NODAGA-galacto-BBN was the highest at 2 weeks, followed by its decrease at 5 and 11 weeks after irradiation, which matched with the expression of GRPR and was more accurately predicted than [ 18 F]F-FDG. These uptake results were also confirmed by the cell uptake assay. Furthermore, [ 64 Cu]Cu-NODAGA-galacto-BBN could monitor the therapeutic efficacy of pirfenidone in RIPF mice. We conclude that [ 64 Cu]Cu-NODAGA-galacto-BBN is a novel PET imaging probe for the early prediction of RIPF-targeting GRPR expressed during the inflammatory response.

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Immediate Release of Gastrin-Releasing Peptide Mediates Delayed Radiation-Induced Pulmonary Fibrosis

Cited by 9 publications

References 45 publications

Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities

Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities

Urine gastrin‐releasing peptide in the first week correlates with bronchopulmonary dysplasia and post‐prematurity respiratory disease

Early Prediction of Radiation-Induced Pulmonary Fibrosis Using Gastrin-Releasing Peptide Receptor-Targeted PET Imaging

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