Budesonide Inhibits Intracellular Infection with Non-Typeable Haemophilus influenzae Despite Its Anti-Inflammatory Effects in Respiratory Cells and Human Lung Tissue: A Role for p38 MAP Kinase.

Abstract

BACKGROUND:

Inhaled corticosteroids (ICS) are widely used in the treatment of obstructive lung diseases. Recent data suggest a higher pneumonia risk in chronic obstructive pulmonary disease (COPD) patients treated with ICS.

OBJECTIVE:

Since non-typeable Haemophilus influenzae (NTHi) is the most common pathogen associated with acute exacerbations of COPD, we investigated the effects of budesonide (BUD) on NTHi-induced inflammation and invasive infection.

METHODS:

The alveolar epithelial cell line A549 and specimens of human lung tissue (HLT) were used in our experiments. Intracellular infection was determined by a lysis/culture assay of infected cells. Activated p38 mitogen-associated protein kinase (MAPK) was assessed using Western blotting and immunohistochemistry, expression of toll-like receptor 2 (TLR2) was determined by PCR, and CXCL-8 levels were measured using ELISA. Immunohistochemistry was used for detection of CXCL-8, platelet-activating factor receptor (PAF-R) and NTHi.

RESULTS:

BUD significantly reduced CXCL-8 secretion in A549 cells and lung tissue infected with NTHi. Furthermore, BUD decreased the expression of PAF-R in HLT and A549 cells. In A549 cells and HLT, BUD inhibited intracellular infection and - synergistically with NTHi - increased the expression of TLR2 (in A549 cells). TLR2 stimulation did not influence the intracellular infection of A549 cells, but p38 MAPK inhibition resulted in a significant reduction of infection.

CONCLUSION:

The present study adds new insights into the effects of glucocorticoids on pulmonary host defence after NTHi infection. Although the inflammatory response to infection is suppressed by BUD, interestingly, the intracellular infection is also inhibited. This effect seems to depend on the inhibition of p38 MAPK - a key enzyme in many pro-inflammatory pathways - as well as of PAF-R expression.

• Authors: Christopher Wagner, Torsten Goldmann, Kristina Rohmann, Jan Rupp, Sebastian Marwitz, Johannes Rotta Detto Loria, Stefan Limmer, Peter Zabel, Klaus Dalhoff, Daniel Drömann
• Journal: Respiration; international review of thoracic diseases (Respiration) Vol. 90 Issue 5 Pg. 416-25 ( 2015) ISSN: 1423-0356 [Electronic] Switzerland
• PMID: 26452008 (Publication Type: Journal Article)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Anti-Inflammatory Agents
• Culture Media, Conditioned
• Budesonide
• p38 Mitogen-Activated Protein Kinases

Topics

• Administration, Inhalation
• Anti-Inflammatory Agents (pharmacology)
• Blotting, Western
• Budesonide (adverse effects, pharmacology)
• Cells, Cultured
• Culture Media, Conditioned
• Enzyme Induction (drug effects)
• Enzyme-Linked Immunosorbent Assay
• Epithelial Cells (drug effects)
• Haemophilus Infections (etiology, physiopathology)
• Haemophilus influenzae (drug effects)
• Humans
• Immunohistochemistry
• Polymerase Chain Reaction
• Pulmonary Disease, Chronic Obstructive (drug therapy, microbiology)
• Sensitivity and Specificity
• p38 Mitogen-Activated Protein Kinases (drug effects, metabolism)