Ras and Mitogen-Activated Protein Kinase Kinase Kinase-1 Coregulate Activator Protein-1– and Nuclear Factor-κB–Mediated Gene Expression in Airway Epithelial Cells

2003 ◽  
Vol 28 (6) ◽  
pp. 762-769 ◽  
Author(s):  
Limei Zhou ◽  
Alan Tan ◽  
Svetlana Iasvovskaia ◽  
Jing Li ◽  
Anning Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Nuclear Factor Κb ◽  
Airway Epithelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Airway Epithelial ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

scholarly journals Uteroglobin Represses Allergen-induced Inflammatory Response by Blocking PGD2 Receptor–mediated Functions

2004 ◽  
Vol 199 (10) ◽  
pp. 1317-1330 ◽  
Author(s):  
Asim K. Mandal ◽  
Zhongjian Zhang ◽  
Rabindranath Ray ◽  
Moonsuk S. Choi ◽  
Bhabadeb Chowdhury ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Inflammatory Response ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Eosinophil Infiltration ◽  
Prostaglandin D2 ◽  
Nuclear Factor ◽  
Mitogen Activated Protein ◽  
Cox 2

Uteroglobin (UG) is an antiinflammatory protein secreted by the epithelial lining of all organs communicating with the external environment. We reported previously that UG-knockout mice manifest exaggerated inflammatory response to allergen, characterized by increased eotaxin and Th2 cytokine gene expression, and eosinophil infiltration in the lungs. In this study, we uncovered that the airway epithelia of these mice also express high levels of cyclooxygenase (COX)-2, a key enzyme for the production of proinflammatory lipid mediators, and the bronchoalveolar lavage fluid (BALF) contain elevated levels of prostaglandin D2. These effects are abrogated by recombinant UG treatment. Although it has been reported that prostaglandin D2 mediates allergic inflammation via its receptor, DP, neither the molecular mechanism(s) of DP signaling nor the mechanism by which UG suppresses DP-mediated inflammatory response are clearly understood. Here we report that DP signaling is mediated via p38 mitogen–activated protein kinase, p44/42 mitogen–activated protein kinase, and protein kinase C pathways in a cell type–specific manner leading to nuclear factor–κB activation stimulating COX-2 gene expression. Further, we found that recombinant UG blocks DP-mediated nuclear factor–κB activation and suppresses COX-2 gene expression. We propose that UG is an essential component of a novel innate homeostatic mechanism in the mammalian airways to repress allergen-induced inflammatory responses.

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