PURPOSE: Keratinocyte growth factor-2 (KGF-2) was known to play an essential role during lung development, but its role in the regulation of acute lung injury is not well defined. We investigated the effects of recombinant human keratinocyte growth factor-2 (rhKGF-2) on acute lung inflammatory injury induced by lipopolysacchride (LPS) in rat lungs.
METHODS: Acute lung injury was induced by intratracheal instillation of bacterial LPS into rats. RhKGF-2 (5 mg/kg) was Intratracheally instilled 3 days before LPS challenge. Lung inflammatory injury was measured by lung wet-to-dry weight ratio, protein leakage into lungs, leukocytes in bronchoalveolar lavage fluid (BALF), and histological analysis. TNF-α and MIP-2 protein levels in BALF was measured. IL-1β and IL-6 mRNA expression levels in lung tissue was also determined by real-time PCR.
RESULTS: Pretreatment of rhKGF-2 resulted in a significant reduction in lung wet-to-dry weight ratio, protein leakage into lungs, and lung injury score when compared to LPS challenged and vehicle pretreated rats. Infiltration of neutrophils in lung tissue and number of neutropils in BALF were also decreased in rats with rhKGF-2 pretreatment. And markedly decreased levels of TNF-α, MIP-2 in BALF and IL-1β, IL-6 mRNA in lung tissue were noted in the rhKGF-2 pretreated rats.
CONCLUSION: Topical administration of rhKGF-2 attenuates lung inflammatory injury induced by LPS. It appears that rhKGF-2 affects the lung inflammatory response by regulating pro-inflammatory cytokines and chemokines production.
CLINICAL IMPLICATIONS: RhKGF-2 may be potent as a novel strategy to the treatment of acute lung injury/acute respiratory distress syndrome.
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