Anti-inflammatory effects of Tat-Annexin protein on ovalbumin-induced airway inflammation in a mouse model of asthma

Biochem Biophys Res Commun. 2012 Jan 20;417(3):1024-9. doi: 10.1016/j.bbrc.2011.12.084. Epub 2011 Dec 26.

Abstract

Chronic airway inflammation is a key feature of bronchial asthma. Annexin-1 (ANX1) is an anti-inflammatory protein that is an important modulator and plays a key role in inflammation. Although the precise action of ANX1 remains unclear, it has emerged as a potential drug target for inflammatory diseases such as asthma. To examine the protective effects of ANX1 protein on ovalbumin (OVA)-induced asthma in animal models, we used a cell-permeable Tat-ANX1 protein. Mice sensitized and challenged with OVA antigen had an increased amount of cytokines and eosinophils in their bronchoalveolar lavage (BAL) fluid. However, administration of Tat-ANX1 protein before OVA challenge significantly decreased the levels of cytokines (interleukin (IL)-4, IL-5, and IL-13) and BAL fluid in lung tissues. Furthermore, OVA significantly increased the activation of mitogen-activated protein kinase (MAPK) in lung tissues, whereas Tat-ANX1 protein markedly reduced phosphorylation of MAPKs such as extracellular signal-regulated protein kinase, p38, and stress-activated protein kinase/c-Jun N-terminal kinase. These results suggest that transduced Tat-ANX1 protein may be a potential protein therapeutic agent for the treatment of lung disorders including asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A1 / administration & dosage
  • Annexin A1 / therapeutic use*
  • Annexins / administration & dosage
  • Annexins / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / prevention & control
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis
  • Disease Models, Animal
  • Female
  • Gene Products, tat / administration & dosage
  • Gene Products, tat / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / therapeutic use*

Substances

  • Annexin A1
  • Annexins
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Gene Products, tat
  • Recombinant Fusion Proteins
  • Tat-ANX1 fusion protein
  • Ovalbumin