Hemokinin-1 is an important mediator of endotoxin-induced acute airway inflammation in the mouse

Zsófia Hajna, Éva Borbély, Ágnes Kemény, Bálint Botz, L. Kereskai, J. Szolcsányi, E. Pintér, Christopher J. Paige, Alexandra Berger, Z. Helyes

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective Hemokinin-1, the newest tachykinin encoded by the preprotachykinin C (Tac4) gene, is predominatly produced by immune cells. Similarly to substance P, it has the greatest affinity to the tachykinin NK1 receptor, but has different binding site and signaling mechanisms. Furthermore, several recent data indicate the existence of a not yet identified own receptor and divergent non-NK1-mediated actions. Since there is no information on its functions in the airways, we investigated its role in endotoxin-induced pulmonary inflammation. Methods Acute pneumonitis was induced in Tac4 gene-deleted (Tac4-/-) mice compared to C57Bl/6 wildtypes by intranasal E. coli lipopolysaccharide (LPS). Airway responsiveness to inhaled carbachol was measured with unrestrained whole body plethysmography 24 h later. Semiquantitative histopathological scoring was performed; reactive oxygen species (ROS) production was measured with luminol bioluminescence, myeloperoxidase activity with spectrophotometry, and inflammatory cytokines with Luminex. Results All inflammatory parameters, such as histopathological alterations (perivascular edema, neutrophil/macrophage accumulation, goblet cell hyperplasia), myeloperoxidase activity, ROS production, as well as interleukin-1beta, interleukin-6, tumor necrosis factor alpha, monocyte chemoattractant protein-1 and keratinocyte chemoattractant concentrations were significantly diminished in the lung of Tac4-/- mice. However, bronchial hyperreactivity similarly developed in both groups. Interestingly, in LPS-treated Tac4-/- mouse lungs, bronchus-associated, large, follicle-like lymphoid structures developed. Conclusions We provide the first evidence that hemokinin-1 plays a crucial pro-inflammatory role in the lung by increasing inflammatory cell activities, and might also be a specific regulator of lymphocyte functions.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalPeptides
Volume64
DOIs
Publication statusPublished - 2015

Fingerprint

Endotoxins
Genes
Inflammation
Tachykinins
Lung
Peroxidase
Lipopolysaccharides
Reactive Oxygen Species
Pneumonia
Whole Body Plethysmography
Plethysmography
Tachykinin Receptors
Bioluminescence
Bronchial Hyperreactivity
Luminol
Goblet Cells
Lymphocytes
Chemokine CCL2
Macrophages
Spectrophotometry

Keywords

  • Acute pneumonitis
  • Luminescence imaging
  • Reactive oxygen species
  • Tachykinin

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

Hemokinin-1 is an important mediator of endotoxin-induced acute airway inflammation in the mouse. / Hajna, Zsófia; Borbély, Éva; Kemény, Ágnes; Botz, Bálint; Kereskai, L.; Szolcsányi, J.; Pintér, E.; Paige, Christopher J.; Berger, Alexandra; Helyes, Z.

In: Peptides, Vol. 64, 2015, p. 1-7.

Research output: Contribution to journalArticle

Hajna, Zsófia ; Borbély, Éva ; Kemény, Ágnes ; Botz, Bálint ; Kereskai, L. ; Szolcsányi, J. ; Pintér, E. ; Paige, Christopher J. ; Berger, Alexandra ; Helyes, Z. / Hemokinin-1 is an important mediator of endotoxin-induced acute airway inflammation in the mouse. In: Peptides. 2015 ; Vol. 64. pp. 1-7.
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abstract = "Objective Hemokinin-1, the newest tachykinin encoded by the preprotachykinin C (Tac4) gene, is predominatly produced by immune cells. Similarly to substance P, it has the greatest affinity to the tachykinin NK1 receptor, but has different binding site and signaling mechanisms. Furthermore, several recent data indicate the existence of a not yet identified own receptor and divergent non-NK1-mediated actions. Since there is no information on its functions in the airways, we investigated its role in endotoxin-induced pulmonary inflammation. Methods Acute pneumonitis was induced in Tac4 gene-deleted (Tac4-/-) mice compared to C57Bl/6 wildtypes by intranasal E. coli lipopolysaccharide (LPS). Airway responsiveness to inhaled carbachol was measured with unrestrained whole body plethysmography 24 h later. Semiquantitative histopathological scoring was performed; reactive oxygen species (ROS) production was measured with luminol bioluminescence, myeloperoxidase activity with spectrophotometry, and inflammatory cytokines with Luminex. Results All inflammatory parameters, such as histopathological alterations (perivascular edema, neutrophil/macrophage accumulation, goblet cell hyperplasia), myeloperoxidase activity, ROS production, as well as interleukin-1beta, interleukin-6, tumor necrosis factor alpha, monocyte chemoattractant protein-1 and keratinocyte chemoattractant concentrations were significantly diminished in the lung of Tac4-/- mice. However, bronchial hyperreactivity similarly developed in both groups. Interestingly, in LPS-treated Tac4-/- mouse lungs, bronchus-associated, large, follicle-like lymphoid structures developed. Conclusions We provide the first evidence that hemokinin-1 plays a crucial pro-inflammatory role in the lung by increasing inflammatory cell activities, and might also be a specific regulator of lymphocyte functions.",
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T1 - Hemokinin-1 is an important mediator of endotoxin-induced acute airway inflammation in the mouse

AU - Hajna, Zsófia

AU - Borbély, Éva

AU - Kemény, Ágnes

AU - Botz, Bálint

AU - Kereskai, L.

AU - Szolcsányi, J.

AU - Pintér, E.

AU - Paige, Christopher J.

AU - Berger, Alexandra

AU - Helyes, Z.

PY - 2015

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N2 - Objective Hemokinin-1, the newest tachykinin encoded by the preprotachykinin C (Tac4) gene, is predominatly produced by immune cells. Similarly to substance P, it has the greatest affinity to the tachykinin NK1 receptor, but has different binding site and signaling mechanisms. Furthermore, several recent data indicate the existence of a not yet identified own receptor and divergent non-NK1-mediated actions. Since there is no information on its functions in the airways, we investigated its role in endotoxin-induced pulmonary inflammation. Methods Acute pneumonitis was induced in Tac4 gene-deleted (Tac4-/-) mice compared to C57Bl/6 wildtypes by intranasal E. coli lipopolysaccharide (LPS). Airway responsiveness to inhaled carbachol was measured with unrestrained whole body plethysmography 24 h later. Semiquantitative histopathological scoring was performed; reactive oxygen species (ROS) production was measured with luminol bioluminescence, myeloperoxidase activity with spectrophotometry, and inflammatory cytokines with Luminex. Results All inflammatory parameters, such as histopathological alterations (perivascular edema, neutrophil/macrophage accumulation, goblet cell hyperplasia), myeloperoxidase activity, ROS production, as well as interleukin-1beta, interleukin-6, tumor necrosis factor alpha, monocyte chemoattractant protein-1 and keratinocyte chemoattractant concentrations were significantly diminished in the lung of Tac4-/- mice. However, bronchial hyperreactivity similarly developed in both groups. Interestingly, in LPS-treated Tac4-/- mouse lungs, bronchus-associated, large, follicle-like lymphoid structures developed. Conclusions We provide the first evidence that hemokinin-1 plays a crucial pro-inflammatory role in the lung by increasing inflammatory cell activities, and might also be a specific regulator of lymphocyte functions.

AB - Objective Hemokinin-1, the newest tachykinin encoded by the preprotachykinin C (Tac4) gene, is predominatly produced by immune cells. Similarly to substance P, it has the greatest affinity to the tachykinin NK1 receptor, but has different binding site and signaling mechanisms. Furthermore, several recent data indicate the existence of a not yet identified own receptor and divergent non-NK1-mediated actions. Since there is no information on its functions in the airways, we investigated its role in endotoxin-induced pulmonary inflammation. Methods Acute pneumonitis was induced in Tac4 gene-deleted (Tac4-/-) mice compared to C57Bl/6 wildtypes by intranasal E. coli lipopolysaccharide (LPS). Airway responsiveness to inhaled carbachol was measured with unrestrained whole body plethysmography 24 h later. Semiquantitative histopathological scoring was performed; reactive oxygen species (ROS) production was measured with luminol bioluminescence, myeloperoxidase activity with spectrophotometry, and inflammatory cytokines with Luminex. Results All inflammatory parameters, such as histopathological alterations (perivascular edema, neutrophil/macrophage accumulation, goblet cell hyperplasia), myeloperoxidase activity, ROS production, as well as interleukin-1beta, interleukin-6, tumor necrosis factor alpha, monocyte chemoattractant protein-1 and keratinocyte chemoattractant concentrations were significantly diminished in the lung of Tac4-/- mice. However, bronchial hyperreactivity similarly developed in both groups. Interestingly, in LPS-treated Tac4-/- mouse lungs, bronchus-associated, large, follicle-like lymphoid structures developed. Conclusions We provide the first evidence that hemokinin-1 plays a crucial pro-inflammatory role in the lung by increasing inflammatory cell activities, and might also be a specific regulator of lymphocyte functions.

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