肺与呼吸系统医学

Mice Lacking Epithelial I-?B Kinase are Protected from Lipopolysaccharide and Cigarette Smoke Extract Induced Inflammation

Abstract

David Lamb, Nicole Parker, Kristina Ulrich, Gareth Jones, Coralie Afeldorfer, Manolis Pasparakis, Steven Evans and Iain Kilty

Background: IKK-2 activity is essential for cytokine mediated NFκB activation and subsequent expression of a wide variety of inflammatory genes. To investigate the role of IKK-2 signalling in lung epithelium we have developed a knock out mouse in which we have specifically deleted the IKK-2 gene in lung epithelial cells.

Materials and Methods: IKK-2 KO mice and littermate control animals were challenged with either nebulised Lipopolysaccharide (LPS) or with Cigarette Smoke Extract (CSE). Cytokines and inflammatory cells were assessed in Bronchoalveolar Lavage Fluid (BALF) and tissue inflammatory cells, markers of apoptosis and general pathology assessed histologically.

Results: BALF neutrophils were reduced by 63% at 4 hours and 67% at 8 hours following LPS challenge in the IKK-2 KO animals (P<0.001). Immunocytochemical analysis showed no difference in neutrophil numbers within pulmonary tissue between the groups or any evidence of increased apoptosis. BALF neutrophils were also reduced below control values in the IKK-2 KO mice in response to CSE compared to littermates animals (P<0.005).

Conclusion: Mice lacking IKK-2 in the pulmonary epithelium recruit fewer neutrophils into the airways in response to both LPS and CSE challenge, suggesting that the epithelium participates in airway inflammatory neutrophil recruitment in response to inflammatory challenge.