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Intranasal curcumin protects against LPS-induced airway remodeling by modulating toll-like receptor-4 (TLR-4) and matrixmetalloproteinase-9 (MMP-9) expression via affecting MAP kinases in mouse model

  • Asha Kumari
  • D. K. Singh
  • D. Dash
  • Rashmi SinghEmail author
Original Article

Abstract

Objective

Bacterial infections can exacerbate asthmatic inflammation depending on lipopolysaccharide (LPS) composition, the outermost component of cell wall, its exposure timings as well as host’s immune status. In present study, Balb/c mice were exposed to antigen (ovalbumin) and LPS simultaneously to establish an asthmatic model. Curcumin (diferuloylmethane), well known for its anti-inflammatory potential, was administered through intranasal route 1 h before LPS and OVA (ovalbumin) exposure to evaluate its efficacy against airway structural changes.

Methods

Inflammatory cell infiltration in lungs was measured by flow cytometry and further eosinophils were especially measured by immunofluorescence detection of major basic protein (MBP) as marker of eosinophilc granule protein. We also measured reactive oxygen species (ROS) in BALF by spectrofluorometry. MMP-9 activity was evaluated by gelatin zymography and mRNA expressions of MMP-9, TIMP-1, TGF-β1, IL-13, Collagen-1 and TLR-4 were measured in lungs. Protein expression of MAP kinases (P-ERK, P-JNK, P-p38), TLR-4, Cox-2, Lox-5 and Eotaxin was measured by western blotting. Hydroxyproline level and masson’s trichrome staining were used to evaluate collagen deposition in lung.

Results

Exposure to LPS (0.1 µg) exacerbates airway inflammation and induces structural changes in lungs by enhanced ROS production, collagen deposition, expression of genes involved in airway remodeling and activation of MAP kinases pathway enzymes. Intranasal curcumin pretreatment had significantly suppressed inflammatory mediators and airway remodeling proteins.

Conclusion

Our results strongly suggest that intranasal curcumin effectively protects LPS-induced airway inflammation and structural changes by modulating genes involved in airway remodeling in safer way; hence, it can be considered as supplementary alternative towards asthma treatments.

Keywords

Asthma exacerbations Sensitization Lipopolysaccharide Airway remodeling Collagen 

Notes

Acknowledgements

This work was supported by Department of Science and Technology-Science and Engineering Research Board, New Delhi, India (DST-SERB). Real time PCR (ABI 7500) and flow cytometer (FACS Calibur, BD Biosciences) studies were performed at Central facility of Interdisciplinary Institute of Life Sciences (ISLS), Banaras Hindu University, Varanasi India.

Compliance with ethical standards

Conflict of interest

Authors have no conflict of interest.

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Asha Kumari
    • 1
  • D. K. Singh
    • 2
  • D. Dash
    • 3
  • Rashmi Singh
    • 1
  1. 1.Department of ZoologyMMV, Banaras Hindu UniversityVaranasiIndia
  2. 2.Department of PhysicsUdai Pratap Autonomous CollegeVaranasiIndia
  3. 3.Department of Biochemistry, Institute of Medical SciencesBanaras Hindu UniversityVaranasiIndia

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