The strong interrelated research themes and common investigative interests of the scientists in this renewal application have served as the key underpins for nearly 15 years of productive and collaborative research under the auspices of this Program Project. These collaborative interaction of the individual research sections continued to promote the unified research objectives: To understand the mechanisms whereby various inflammatory mediators contribute to their initiation, maintenance, and resolution of acute an chronic lung inflammation and injury. The strategy for the individual projects, using well established experimental models, will include a cellular and molecular approach to determine the mechanistic contribution of novel adhesion molecules, chemokines, and regulatory cytokines in cute immune complex-induced lung injury and to assess the contribution of chemokines and their receptors to the initiation and maintenance of chronic cell-mediated pulmonary inflammation caused by specific type 1 or type 2 cytokines using experimental models which include chemokine receptor knockout mice (Section II, Steven L. Kunkel, Ph.D.); to determine the role of eosinophils in chemokine-cytokine dependent networks which are responsible for collagen deposition and pulmonary fibrosis by assessing monocyte chemotactic protein-1 induction pf transforming growth factor beta1 (Sem H. Phan, M.D., Ph.D.); and to investigate the mechanisms whereby chemokines and their specific receptors promote leukocyte activation and elicitation during allergen-induced pulmonary airway hyper-reactivity using cockroach antigen as a clinically important allergen (Nicholas W. Lukacs, Ph.D.). These sections will be supported by an administrative core Peter A. Ward, M.D.) and a morphology core (Kent Johnson, M.D.) to aid in coordinating financial matters and assist in the execution of morphology/morphometric studies, respectively. Thus, the rationale of this Program Project is to focus the combined experience of investigators with established collaborative interactions and proven chemokines and chemokine receptors contribute to lung inflammation and injury. The proposed studies found in this Program Project will provide insight into mechanisms which dictate the progression of inflammatory lung disease and aid in the development of novel therapeutic strategies.
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