Dexamethasone Attenuates LPS-induced Acute Lung Injury through Inhibition of NF-κB, COX-2, and Pro-inflammatory Mediators.

Abstract

Dexamethasone (DEX) is a synthetic glucocorticoid with potent anti-inflammatory effects that is widely used to treat inflammatory diseases. The aim of the present study was to investigate the possible protective effect of DEX on the lipopolysaccharides (LPS)-induced acute lung injury (ALI) in a mouse model. Animals were pretreated with DEX (5 and 10 mg/kg, i.p.) for seven days and acute lung injury was induced by intranasal (i.n.) administration of LPS on day 7. In the present study, administration of LPS resulted in significant increase in neutrophils and lymphocytes count whereas a substantial reduction in T cell subsets (CD3(+) and CD4(+)) and pro-inflammatory (IL-6 and TNF-α) cytokines occurred, which were reversed by DEX treatment. RT-PCR analysis revealed an increased mRNA expression of IL-6, TNF-α, COX-2, iNOS, and NF-κB p65 and decreased IL-10 in the LPS group, which were reversed by treatment with DEX in lung tissues. Western blot analysis revealed an increased expression of COX-2, iNOS and NF-κB p65 in the LPS-group, which was reduced by treatment with DEX. Compared with the LPS group, the DEX treatment also demonstrated a considerable increase in the protein expression level of IL-10 cytokine. Administration of LPS resulted in marked increase in malondialdehyde (MDA) levels and myeloperoxidase (MPO) activity whereas noticeable decrease in glutathione (GSH) content. These changes were significantly reversed by treatment with DEX. The histological examinations revealed protective effect of DEX while LPS group aggravated lung injury. The present findings demonstrate the potent anti-inflammatory action of the DEX against acute lung injury induced by LPS.

• Authors: Naif O Al-Harbi, Faisal Imam, Mohammed M Al-Harbi, Mushtaq Ahmad Ansari, Khairy M A Zoheir, Hesham M Korashy, Mohamed M Sayed-Ahmed, Sabry M Attia, Othman A Shabanah, Sheikh Fayaz Ahmad
• Journal: Immunological investigations (Immunol Invest) Vol. 45 Issue 4 Pg. 349-69 (May 2016) ISSN: 1532-4311 [Electronic] England
• PMID: 27104958 (Publication Type: Journal Article)

Chemical References

• Inflammation Mediators
• Interleukin-6
• Lipopolysaccharides
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Dexamethasone
• Cyclooxygenase 2

Topics

• Acute Lung Injury (drug therapy)
• Animals
• Cells, Cultured
• Cyclooxygenase 2 (genetics, metabolism)
• Dexamethasone (therapeutic use)
• Humans
• Inflammation Mediators (metabolism)
• Interleukin-10 (genetics, metabolism)
• Interleukin-6 (genetics, metabolism)
• Lipopolysaccharides (immunology)
• Lung (drug effects, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• NF-kappa B (genetics, metabolism)
• Neutrophils (drug effects, immunology)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (genetics, metabolism)