Coordinated post-transcriptional regulation of the chemokine system: messages from CCL2.
The molecular cross-talk between epithelium and immune cells in the airway mucosa is a key regulator of homeostatic immune surveillance and is crucially involved in the development of chronic lung inflammatory diseases. The patterns of gene expression that follow the sensitization process occurring in allergic asthma and chronic rhinosinusitis and those present in the neutrophilic response of other chronic inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD) are tightly regulated in their specificity. Studies exploring the global transcript profiles associated with determinants of post-transcriptional gene regulation (PTR) such as RNA-binding proteins (RBP) and microRNAs identified several of these factors as being crucially involved in controlling the expression of chemokines upon airway epithelial cell stimulation with cytokines prototypic of Th1- or Th2-driven responses. These studies also uncovered the participation of these pathways to glucocorticoids' inhibitory effect on the epithelial chemokine network. Unmasking the molecular mechanisms of chemokine PTR may likely uncover novel therapeutic strategies for the blockade of proinflammatory pathways that are pathogenetic for asthma, COPD, and other lung inflammatory diseases.
1 Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine , Hershey, Pennsylvania.
Ronaldo P
RP
Panganiban
Becky M
BM
Vonakis
Faoud T
FT
Ishmael
Cristiana
C
Stellato
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020239:Receptor Cross-Talk; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D059467:Transcriptome
D018932:Chemokine CCL2; D035683:MicroRNAs; D016601:RNA-Binding Proteins