Oxytetracycline attenuates allergic airway inflammation in mice via inhibition of the NF-κB pathway.
Oxytetracycline has been used in the treatment of acute and chronic bronchial inflammation and infectious asthma. However, its potential use for non-infectious asthma has not yet been studied. The objective of this study was to investigate the anti-inflammatory properties of oxytetracycline using a mouse asthma model. Female BALB/c mice, sensitized and challenged with ovalbumin. Naive CD4+ T cells from spleen were stimulated for 72 h with anti-CD3 (5 μg/ml) plus anti-CD28 (2.5 μg/ml) and differentiated into Th2 cells. IL-4, IL-5, IL-9, IL-13, and ovalbumin (OVA)-specific IgE production were measured by ELISA in BALF and cell supernatants. Histopathological evaluation was used to study the alterations in lung tissue. The mRNA levels of CCL5, CCL11, CCR1, and CCR3 were detected by real-time PCR. In addition, the protein levels of p-Akt, Akt, nuclear factor kappa B (NF-κB), IκBα and p-IκBα in lung tissue and cells were measured by western blot or immunofluorescence analysis. Oxytetracycline treatment caused a marked reduction in IL-4, IL-5, IL-13, immune cells, and the level of ovalbumin-specific IgE. Real-time PCR studies demonstrated that oxytetracycline can significantly reduce CCL5, CCL11 and their specific receptor CCR1 and CCR3. Histological studies demonstrated that oxytetracycline substantially inhibited ovalbumin-induced inflammatory cell infiltration in lung tissue and goblet cell hyperplasia in airway. Oxytetracycline inhibited the NF-κB activation via phosphorylation and degradation of IκBα both in vivo and in vitro. Furthermore, the increased phosphorylated Akt but not Akt protein levels in lung tissues after OVA inhalation were significantly reduced by the oral administration of oxytetracycline. These findings demonstrate an anti-inflammatory effect of oxytetracycline that might be mediated via reduction of inflammatory mediators and activation of transcription factors.
Institute of Zoonoses, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, People's Republic of China.
Xinxin
X
Ci
Xiao
X
Chu
Chi
C
Chen
Xiangchao
X
Li
Shuhan
S
Yan
Xinrui
X
Wang
Yongjun
Y
Yang
Xuming
X
Deng
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D020672:I-kappa B Proteins / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D010118:Oxytetracycline / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D012137:Respiratory System / Q000187:drug effects* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D000097782:NF-kappaB-Inducing Kinase
D018927:Anti-Asthmatic Agents; D016207:Cytokines; D020672:I-kappa B Proteins; D007073:Immunoglobulin E; D016328:NF-kappa B; D010047:Ovalbumin; D010118:Oxytetracycline; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000097782:NF-kappaB-Inducing Kinase