Tn (N-acetyl-D-galactosamine-O-serine/threonine) immunization protects against hyperoxia-induced lung injury in adult mice through inhibition of the nuclear factor kappa B activity

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Abstract

Prolonged hyperoxia exposure leads to inflammation and acute lung injury. Since hyperoxia activates nuclear factor kappa B (NF-κB) and proinflammatory mediators in lung fibroblasts and murine lungs, and proinflammatory cytokines upregulate Tn (N-acetyl-D-galactosamine-O-serine/threonine) expression in human gingival fibroblasts. We hypothesized connections exist between Tn expression and inflammation regulation. Thus, we immunized adult mice with Tn antigen to examine whether Tn vaccine can protect against hyperoxia-induced lung injury by inhibiting NF-κB activity and cytokine expression through the action of anti-Tn antibodies. Five-week-old female C57BL/6NCrlBltw mice were subcutaneously immunized with Tn antigen four times at biweekly intervals, and one additional immunization was performed at 1 week after the fourth immunization. Four days after the last immunization, mice were exposed to room air (RA) or hyperoxia (100% O2) for up to 96 h. Four study groups were examined: carrier protein + RA (n = 6), Tn vaccine + RA (n = 6), carrier protein + O2 (n = 6), and Tn vaccine + O2 (n = 5). We observed that hyperoxia exposure reduced body weight, increased alveolar protein and cytokine (interleukin-6 and tumor necrosis factor-α) levels, increased mean linear intercept (MLI) values and lung injury scores, and increased lung NF-κB activity. By contrast, Tn immunization increased serum anti-Tn antibody titers and reduced the cytokine levels, MLI values, and lung injury scores. Furthermore, the alleviation of lung injury was accompanied by a reduction in NF-κB activity. Therefore, we proposed that Tn immunization attenuates hyperoxia-induced lung injury in adult mice by inhibiting the NF-κB activity.

Original languageEnglish
Pages (from-to)261-268
Number of pages8
JournalInternational Immunopharmacology
Volume59
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

Acetylgalactosamine
Hyperoxia
NF-kappa B
Lung Injury
Threonine
Serine
Immunization
Cytokines
Vaccines
Air
Lung
Anti-Idiotypic Antibodies
Carrier Proteins
Fibroblasts
Inflammation
Acute Lung Injury
Inbred C57BL Mouse
Interleukin-6
Up-Regulation
Tumor Necrosis Factor-alpha

Keywords

  • Hyperoxia
  • Interleukin-6
  • Mean linear intercept
  • Tumor necrosis factor-α
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

@article{3ef794b4787d4e06bbb8da55d16e61ab,
title = "Tn (N-acetyl-D-galactosamine-O-serine/threonine) immunization protects against hyperoxia-induced lung injury in adult mice through inhibition of the nuclear factor kappa B activity",
abstract = "Prolonged hyperoxia exposure leads to inflammation and acute lung injury. Since hyperoxia activates nuclear factor kappa B (NF-κB) and proinflammatory mediators in lung fibroblasts and murine lungs, and proinflammatory cytokines upregulate Tn (N-acetyl-D-galactosamine-O-serine/threonine) expression in human gingival fibroblasts. We hypothesized connections exist between Tn expression and inflammation regulation. Thus, we immunized adult mice with Tn antigen to examine whether Tn vaccine can protect against hyperoxia-induced lung injury by inhibiting NF-κB activity and cytokine expression through the action of anti-Tn antibodies. Five-week-old female C57BL/6NCrlBltw mice were subcutaneously immunized with Tn antigen four times at biweekly intervals, and one additional immunization was performed at 1 week after the fourth immunization. Four days after the last immunization, mice were exposed to room air (RA) or hyperoxia (100{\%} O2) for up to 96 h. Four study groups were examined: carrier protein + RA (n = 6), Tn vaccine + RA (n = 6), carrier protein + O2 (n = 6), and Tn vaccine + O2 (n = 5). We observed that hyperoxia exposure reduced body weight, increased alveolar protein and cytokine (interleukin-6 and tumor necrosis factor-α) levels, increased mean linear intercept (MLI) values and lung injury scores, and increased lung NF-κB activity. By contrast, Tn immunization increased serum anti-Tn antibody titers and reduced the cytokine levels, MLI values, and lung injury scores. Furthermore, the alleviation of lung injury was accompanied by a reduction in NF-κB activity. Therefore, we proposed that Tn immunization attenuates hyperoxia-induced lung injury in adult mice by inhibiting the NF-κB activity.",
keywords = "Hyperoxia, Interleukin-6, Mean linear intercept, Tumor necrosis factor-α, Vaccine",
author = "Chen, {Chung Ming} and Jaulang Hwang and Chou, {Hsiu Chu} and Shiah, {Her Shyong}",
year = "2018",
month = "6",
day = "1",
doi = "10.1016/j.intimp.2018.04.022",
language = "English",
volume = "59",
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journal = "International Immunopharmacology",
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T1 - Tn (N-acetyl-D-galactosamine-O-serine/threonine) immunization protects against hyperoxia-induced lung injury in adult mice through inhibition of the nuclear factor kappa B activity

AU - Chen, Chung Ming

AU - Hwang, Jaulang

AU - Chou, Hsiu Chu

AU - Shiah, Her Shyong

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Prolonged hyperoxia exposure leads to inflammation and acute lung injury. Since hyperoxia activates nuclear factor kappa B (NF-κB) and proinflammatory mediators in lung fibroblasts and murine lungs, and proinflammatory cytokines upregulate Tn (N-acetyl-D-galactosamine-O-serine/threonine) expression in human gingival fibroblasts. We hypothesized connections exist between Tn expression and inflammation regulation. Thus, we immunized adult mice with Tn antigen to examine whether Tn vaccine can protect against hyperoxia-induced lung injury by inhibiting NF-κB activity and cytokine expression through the action of anti-Tn antibodies. Five-week-old female C57BL/6NCrlBltw mice were subcutaneously immunized with Tn antigen four times at biweekly intervals, and one additional immunization was performed at 1 week after the fourth immunization. Four days after the last immunization, mice were exposed to room air (RA) or hyperoxia (100% O2) for up to 96 h. Four study groups were examined: carrier protein + RA (n = 6), Tn vaccine + RA (n = 6), carrier protein + O2 (n = 6), and Tn vaccine + O2 (n = 5). We observed that hyperoxia exposure reduced body weight, increased alveolar protein and cytokine (interleukin-6 and tumor necrosis factor-α) levels, increased mean linear intercept (MLI) values and lung injury scores, and increased lung NF-κB activity. By contrast, Tn immunization increased serum anti-Tn antibody titers and reduced the cytokine levels, MLI values, and lung injury scores. Furthermore, the alleviation of lung injury was accompanied by a reduction in NF-κB activity. Therefore, we proposed that Tn immunization attenuates hyperoxia-induced lung injury in adult mice by inhibiting the NF-κB activity.

AB - Prolonged hyperoxia exposure leads to inflammation and acute lung injury. Since hyperoxia activates nuclear factor kappa B (NF-κB) and proinflammatory mediators in lung fibroblasts and murine lungs, and proinflammatory cytokines upregulate Tn (N-acetyl-D-galactosamine-O-serine/threonine) expression in human gingival fibroblasts. We hypothesized connections exist between Tn expression and inflammation regulation. Thus, we immunized adult mice with Tn antigen to examine whether Tn vaccine can protect against hyperoxia-induced lung injury by inhibiting NF-κB activity and cytokine expression through the action of anti-Tn antibodies. Five-week-old female C57BL/6NCrlBltw mice were subcutaneously immunized with Tn antigen four times at biweekly intervals, and one additional immunization was performed at 1 week after the fourth immunization. Four days after the last immunization, mice were exposed to room air (RA) or hyperoxia (100% O2) for up to 96 h. Four study groups were examined: carrier protein + RA (n = 6), Tn vaccine + RA (n = 6), carrier protein + O2 (n = 6), and Tn vaccine + O2 (n = 5). We observed that hyperoxia exposure reduced body weight, increased alveolar protein and cytokine (interleukin-6 and tumor necrosis factor-α) levels, increased mean linear intercept (MLI) values and lung injury scores, and increased lung NF-κB activity. By contrast, Tn immunization increased serum anti-Tn antibody titers and reduced the cytokine levels, MLI values, and lung injury scores. Furthermore, the alleviation of lung injury was accompanied by a reduction in NF-κB activity. Therefore, we proposed that Tn immunization attenuates hyperoxia-induced lung injury in adult mice by inhibiting the NF-κB activity.

KW - Hyperoxia

KW - Interleukin-6

KW - Mean linear intercept

KW - Tumor necrosis factor-α

KW - Vaccine

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